1 00:00:03,300 --> 00:00:09,380 [Music] 2 00:00:15,420 --> 00:00:13,320 I'm gonna run you through a little bit 3 00:00:18,510 --> 00:00:15,430 different scenario than we've had in 4 00:00:20,519 --> 00:00:18,520 this convention so far but just give an 5 00:00:22,260 --> 00:00:20,529 idea of what we're about we have a 6 00:00:24,870 --> 00:00:22,270 technology platform that we call 7 00:00:27,630 --> 00:00:24,880 resonant molecular signaling and it 8 00:00:29,940 --> 00:00:27,640 ought to resonate with this group we're 9 00:00:32,850 --> 00:00:29,950 convinced that good health depends on 10 00:00:35,400 --> 00:00:32,860 typical communication between and 11 00:00:37,620 --> 00:00:35,410 amongst within and among cells any 12 00:00:39,720 --> 00:00:37,630 disruption of that signaling will result 13 00:00:42,810 --> 00:00:39,730 in disease it can be acute like a stroke 14 00:00:45,150 --> 00:00:42,820 or chronic like rheumatoid arthritis our 15 00:00:47,850 --> 00:00:45,160 goal using resident molecular signaling 16 00:00:50,490 --> 00:00:47,860 is simply to use molecules and 17 00:00:52,230 --> 00:00:50,500 oftentimes fractions of molecules to 18 00:00:55,500 --> 00:00:52,240 restore communication and let the body 19 00:00:57,600 --> 00:00:55,510 do what it's supposed to do the 20 00:00:59,760 --> 00:00:57,610 therapeutic agents that we use in 21 00:01:02,430 --> 00:00:59,770 Resident alekhya leur signaling are as a 22 00:01:04,229 --> 00:01:02,440 group selected after studying the 23 00:01:05,910 --> 00:01:04,239 pathophysiology of disease what we're 24 00:01:08,340 --> 00:01:05,920 interested in is we we look at a disease 25 00:01:09,929 --> 00:01:08,350 disease X whatever it might be look at 26 00:01:12,660 --> 00:01:09,939 the sequence of events leading from 27 00:01:14,700 --> 00:01:12,670 initiation of disease to occurrence of 28 00:01:17,010 --> 00:01:14,710 signs and symptoms and see where we can 29 00:01:18,960 --> 00:01:17,020 interfere with that then think about a 30 00:01:21,420 --> 00:01:18,970 molecule that might be able to do that 31 00:01:23,190 --> 00:01:21,430 interference and we come up with these 32 00:01:25,980 --> 00:01:23,200 molecules either just brainstorming 33 00:01:28,950 --> 00:01:25,990 maybe reading the literature or just by 34 00:01:31,469 --> 00:01:28,960 trial and error with one exception all 35 00:01:34,200 --> 00:01:31,479 the molecules we use therapeutically are 36 00:01:36,930 --> 00:01:34,210 naturally occurring they are often well 37 00:01:38,190 --> 00:01:36,940 studied but also with but one exception 38 00:01:40,560 --> 00:01:38,200 they've never been used therapeutically 39 00:01:43,710 --> 00:01:40,570 before so they're all together different 40 00:01:47,100 --> 00:01:43,720 than what's on the market now they are 41 00:01:50,010 --> 00:01:47,110 safe and we have done I think we're into 42 00:01:53,190 --> 00:01:50,020 our sixteenth phase to FDA trial we've 43 00:01:55,710 --> 00:01:53,200 done a couple USDA trials also in all of 44 00:01:57,630 --> 00:01:55,720 those trials to put the safety profile 45 00:01:59,310 --> 00:01:57,640 for the placebo placebo group is the 46 00:02:03,000 --> 00:01:59,320 same as for the treated group so these 47 00:02:04,500 --> 00:02:03,010 things are safe very interesting is they 48 00:02:05,910 --> 00:02:04,510 are stable at all these different 49 00:02:08,070 --> 00:02:05,920 temperatures that's interesting because 50 00:02:10,169 --> 00:02:08,080 some of these molecules are enzymes or 51 00:02:12,809 --> 00:02:10,179 hormones and those of you that work in 52 00:02:15,960 --> 00:02:12,819 biology know that those are not stable 53 00:02:17,100 --> 00:02:15,970 at room temperature or at pocket 54 00:02:18,510 --> 00:02:17,110 temperature things like that they are 55 00:02:20,580 --> 00:02:18,520 not stable with respect to their 56 00:02:22,080 --> 00:02:20,590 enzymatic or hormonal activity but 57 00:02:23,100 --> 00:02:22,090 that's not what we're looking at we're 58 00:02:25,680 --> 00:02:23,110 looking at a different kind of 59 00:02:27,960 --> 00:02:25,690 of activity and we administer these in 60 00:02:33,840 --> 00:02:27,970 what we call physiologic doses much more 61 00:02:35,610 --> 00:02:33,850 concentrated than a remedy that would be 62 00:02:37,640 --> 00:02:35,620 associated with homeopathy but less 63 00:02:41,880 --> 00:02:37,650 concentrated there might be a normal 64 00:02:43,820 --> 00:02:41,890 physiologic rub allopathic dose we're 65 00:02:46,800 --> 00:02:43,830 convinced that these agents that we use 66 00:02:48,450 --> 00:02:46,810 act as nothing more than signals to 67 00:02:50,010 --> 00:02:48,460 stimulate a cascade of events that 68 00:02:51,900 --> 00:02:50,020 results in the desired outcome of 69 00:02:53,970 --> 00:02:51,910 interest is there's no relationship 70 00:02:57,000 --> 00:02:53,980 between patient mass and the dose that 71 00:02:59,790 --> 00:02:57,010 we use so a 2,000 pound horse gets the 72 00:03:03,150 --> 00:02:59,800 same dose as a 5 pound chihuahua or 150 73 00:03:06,240 --> 00:03:03,160 pound man the frequency of dosing can 74 00:03:08,310 --> 00:03:06,250 change but never the dose itself also of 75 00:03:10,860 --> 00:03:08,320 interest is we can use different routes 76 00:03:12,270 --> 00:03:10,870 of administration with the same dose get 77 00:03:14,070 --> 00:03:12,280 the same response in the same amount of 78 00:03:16,320 --> 00:03:14,080 time you can't think of very many 79 00:03:17,970 --> 00:03:16,330 medicines that do that that again give 80 00:03:20,699 --> 00:03:17,980 us a hint that these are simply acting 81 00:03:23,250 --> 00:03:20,709 as signals what I want to do today is 82 00:03:25,199 --> 00:03:23,260 focus on just one of these therapeutic 83 00:03:27,630 --> 00:03:25,209 agents as kind of the prototype for our 84 00:03:29,370 --> 00:03:27,640 platform and this is streptomycin oh 85 00:03:31,620 --> 00:03:29,380 that's scribble on the right is supposed 86 00:03:32,910 --> 00:03:31,630 to resemble three-dimensional structure 87 00:03:34,920 --> 00:03:32,920 of streptomycin though I don't know if 88 00:03:36,770 --> 00:03:34,930 it does or not I've never seen it but 89 00:03:39,030 --> 00:03:36,780 that's what comes out of the literature 90 00:03:41,220 --> 00:03:39,040 this is a molecule that you're all 91 00:03:43,520 --> 00:03:41,230 familiar with one way or another this is 92 00:03:46,020 --> 00:03:43,530 the toxin from group a beta hemolytic 93 00:03:48,720 --> 00:03:46,030 streptococcus or throat and this is the 94 00:03:51,090 --> 00:03:48,730 toxin that causes a sore throat we use 95 00:03:55,530 --> 00:03:51,100 it as a therapeutic agent in a little 96 00:03:59,640 --> 00:03:55,540 bit a little bit different situation in 97 00:04:02,490 --> 00:03:59,650 that we modify the toxin we reduce it 98 00:04:04,080 --> 00:04:02,500 it's toxic in its I'm sorry it's toxic 99 00:04:06,570 --> 00:04:04,090 in its reduced state we modify it to the 100 00:04:09,120 --> 00:04:06,580 oxidized state it loses its toxicity and 101 00:04:13,580 --> 00:04:09,130 gains therapeutic activity of a 102 00:04:17,219 --> 00:04:13,590 different way that's the modification 103 00:04:18,630 --> 00:04:17,229 well there we go now one might wonder 104 00:04:20,699 --> 00:04:18,640 what the heck why would we ever use 105 00:04:22,350 --> 00:04:20,709 streptomycin o as a therapeutic agent in 106 00:04:24,960 --> 00:04:22,360 the first place there was a paper 107 00:04:26,730 --> 00:04:24,970 presented oh gosh she's gotta be eight 108 00:04:28,230 --> 00:04:26,740 or nine years ago now by a professor at 109 00:04:32,370 --> 00:04:28,240 Brown University at the Medical School 110 00:04:34,200 --> 00:04:32,380 and this gal did some epidemiological 111 00:04:35,760 --> 00:04:34,210 work to show that movement disorders 112 00:04:36,869 --> 00:04:35,770 like Tourette's and ticks and things 113 00:04:38,429 --> 00:04:36,879 like that 114 00:04:40,980 --> 00:04:38,439 in adults could be related to a 115 00:04:43,589 --> 00:04:40,990 childhood history of chronic or repeated 116 00:04:45,239 --> 00:04:43,599 strep infections we wondered what the 117 00:04:47,699 --> 00:04:45,249 heck could that relationship be that is 118 00:04:49,199 --> 00:04:47,709 clearly the organism was no longer there 119 00:04:52,079 --> 00:04:49,209 in the adult and yet we had these 120 00:04:54,199 --> 00:04:52,089 symptoms what might be happening and we 121 00:04:58,889 --> 00:04:54,209 thought there might be a situation 122 00:05:01,010 --> 00:04:58,899 involved with an aberrant immune 123 00:05:03,119 --> 00:05:01,020 response to the original infection that 124 00:05:06,290 --> 00:05:03,129 persisted through our life and could 125 00:05:09,299 --> 00:05:06,300 cause these problems so what we did was 126 00:05:11,939 --> 00:05:09,309 obtained some very very highly purified 127 00:05:13,769 --> 00:05:11,949 strep to licen though we oxidized it 128 00:05:15,629 --> 00:05:13,779 that's the modification step then we had 129 00:05:18,389 --> 00:05:15,639 to find a patient with this kind of a 130 00:05:20,939 --> 00:05:18,399 problem and we found one of a patient 131 00:05:22,469 --> 00:05:20,949 that was in the the practice of one of 132 00:05:25,619 --> 00:05:22,479 the physicians in our group who had a 133 00:05:27,959 --> 00:05:25,629 horrible tick of the neck and head she 134 00:05:30,119 --> 00:05:27,969 was always going like this about every 6 135 00:05:31,739 --> 00:05:30,129 or 7 seconds if you sat in the 136 00:05:33,439 --> 00:05:31,749 examination room with her within three 137 00:05:36,419 --> 00:05:33,449 or four minutes you're going like this - 138 00:05:39,119 --> 00:05:36,429 everybody's doing this she was 34 years 139 00:05:41,449 --> 00:05:39,129 old at the at the time of initiation of 140 00:05:44,699 --> 00:05:41,459 therapy she was being treated by this 141 00:05:46,619 --> 00:05:44,709 physician for another problem but he 142 00:05:50,850 --> 00:05:46,629 contacted her and said listen Mary would 143 00:05:53,429 --> 00:05:50,860 you be interested in trying this kind of 144 00:05:54,929 --> 00:05:53,439 left-wing wacko approach to seeing if we 145 00:05:56,999 --> 00:05:54,939 could do anything with your tip we're 146 00:05:59,040 --> 00:05:57,009 confident it'll be safe we haven't the 147 00:05:59,429 --> 00:05:59,050 foggiest idea if it's gonna do you any 148 00:06:02,009 --> 00:05:59,439 good 149 00:06:04,439 --> 00:06:02,019 she said yep let's give it a try so she 150 00:06:06,809 --> 00:06:04,449 came to the clinic she was instructed to 151 00:06:09,329 --> 00:06:06,819 take one drop under her tongue of this 152 00:06:11,909 --> 00:06:09,339 modified strep - Lysa no four times a 153 00:06:14,159 --> 00:06:11,919 day come back in four weeks she did that 154 00:06:16,619 --> 00:06:14,169 and at the end of the four weeks she 155 00:06:18,899 --> 00:06:16,629 came back and clearly her tick was 156 00:06:20,429 --> 00:06:18,909 reduced but it was not gone the 157 00:06:21,989 --> 00:06:20,439 physician had the good sense to say well 158 00:06:23,790 --> 00:06:21,999 gosh Mary did you see anything else good 159 00:06:25,499 --> 00:06:23,800 or bad that occurred during this four a 160 00:06:27,899 --> 00:06:25,509 week period and she goes like this 161 00:06:30,839 --> 00:06:27,909 William just about pushes the guy out 162 00:06:33,480 --> 00:06:30,849 she said look at this well yeah close up 163 00:06:35,699 --> 00:06:33,490 and I said it very nice looking fist 164 00:06:38,189 --> 00:06:35,709 what am I looking at and she said well 165 00:06:39,959 --> 00:06:38,199 when I was eight or nine years old I was 166 00:06:42,839 --> 00:06:39,969 in my mother's kitchen and I pulled a 167 00:06:45,089 --> 00:06:42,849 sauce pan of boiling water off the stove 168 00:06:47,040 --> 00:06:45,099 onto my hand and I burned my knuckles 169 00:06:48,389 --> 00:06:47,050 very badly scarred we thought 170 00:06:51,210 --> 00:06:48,399 permanently and in four weeks those 171 00:06:53,610 --> 00:06:51,220 scars are gone well 172 00:06:55,200 --> 00:06:53,620 that's kind of interesting how do you 173 00:06:57,270 --> 00:06:55,210 makes cars go you're taking a drop out 174 00:07:00,410 --> 00:06:57,280 of the tongue and this cows cars 175 00:07:02,880 --> 00:07:00,420 disappear so we thought well geez oh man 176 00:07:06,690 --> 00:07:02,890 that might be kind of interesting all by 177 00:07:08,580 --> 00:07:06,700 itself and we brought other patients in 178 00:07:10,590 --> 00:07:08,590 who had superficial scars of this sort 179 00:07:12,630 --> 00:07:10,600 that we could see and we found that yes 180 00:07:14,730 --> 00:07:12,640 indeed without exception we could 181 00:07:16,110 --> 00:07:14,740 certainly reduce the scars and sometimes 182 00:07:18,570 --> 00:07:16,120 make them go away completely in a 183 00:07:20,880 --> 00:07:18,580 four-week period again taking sublingual 184 00:07:24,750 --> 00:07:20,890 drops and it didn't matter where the 185 00:07:26,820 --> 00:07:24,760 scars were as we got more and more into 186 00:07:29,340 --> 00:07:26,830 this we found that the spectrum of 187 00:07:32,160 --> 00:07:29,350 targets for SLO therapy expanded far 188 00:07:34,230 --> 00:07:32,170 beyond scars and we'll take a look at 189 00:07:36,860 --> 00:07:34,240 some of that you know a little bit later 190 00:07:39,120 --> 00:07:36,870 today but wanted to give you an idea of 191 00:07:40,140 --> 00:07:39,130 some of the problems that we had trying 192 00:07:43,070 --> 00:07:40,150 to get our heads around what the heck's 193 00:07:48,420 --> 00:07:43,080 going on here we said what does SLO do 194 00:07:50,250 --> 00:07:48,430 this little photo micrograph collection 195 00:07:53,310 --> 00:07:50,260 is from collaborative work we did with 196 00:07:54,480 --> 00:07:53,320 investigators at NYU and what we have 197 00:07:57,870 --> 00:07:54,490 here whoops 198 00:08:00,000 --> 00:07:57,880 whichever hand has the pointer what we 199 00:08:02,160 --> 00:08:00,010 have here is human tissue grown on a 200 00:08:04,650 --> 00:08:02,170 microscope slide we cut the tissue was 201 00:08:06,180 --> 00:08:04,660 with a scalpel and then you'll see that 202 00:08:10,260 --> 00:08:06,190 we've used two different concentrations 203 00:08:11,910 --> 00:08:10,270 of slo exposed some cells that is some 204 00:08:14,370 --> 00:08:11,920 microscope some cells on microscope 205 00:08:16,170 --> 00:08:14,380 flies to SLO and have controls here and 206 00:08:19,080 --> 00:08:16,180 what we're measuring is the rate at 207 00:08:22,230 --> 00:08:19,090 which the gap closes this is superficial 208 00:08:24,930 --> 00:08:22,240 healing and what we found was that there 209 00:08:26,730 --> 00:08:24,940 is an incredibly increased rate of 210 00:08:28,800 --> 00:08:26,740 activation mobilization of character 211 00:08:30,030 --> 00:08:28,810 sites that causes closing the gap much 212 00:08:32,909 --> 00:08:30,040 faster than what happened under normal 213 00:08:35,250 --> 00:08:32,919 conditions well great let's go a little 214 00:08:36,839 --> 00:08:35,260 bit deeper in that and see what genes 215 00:08:40,320 --> 00:08:36,849 are up and downregulated is a 216 00:08:41,339 --> 00:08:40,330 consequence of SLO exposure and we're 217 00:08:43,500 --> 00:08:41,349 certainly not going to go through all 218 00:08:46,860 --> 00:08:43,510 this but there are a couple important 219 00:08:51,920 --> 00:08:46,870 things here that you maybe heard of cd44 220 00:08:56,100 --> 00:08:51,930 antigen especially important in aligning 221 00:08:58,290 --> 00:08:56,110 collagen in proper sequence for scar 222 00:09:01,530 --> 00:08:58,300 formation for wound repair and so forth 223 00:09:04,199 --> 00:09:01,540 and we are upregulating that that's an 224 00:09:05,910 --> 00:09:04,209 anti inflammatory cytokine also so 225 00:09:08,850 --> 00:09:05,920 we're getting anti-inflammatory effects 226 00:09:11,730 --> 00:09:08,860 from SLO this one some of you might even 227 00:09:13,859 --> 00:09:11,740 take chondroitin nutritional supplement 228 00:09:16,340 --> 00:09:13,869 if you have arthritis in your knee or a 229 00:09:18,509 --> 00:09:16,350 sore elbow chondroitin is a typical 230 00:09:20,340 --> 00:09:18,519 nutritional supplement for that we think 231 00:09:22,259 --> 00:09:20,350 it's better to induce the body to 232 00:09:23,999 --> 00:09:22,269 generate its own and we can do it with 233 00:09:27,299 --> 00:09:24,009 SLO and a couple other molecules we use 234 00:09:29,299 --> 00:09:27,309 but complementary complementary Carolee 235 00:09:32,669 --> 00:09:29,309 to the upregulation in these 236 00:09:35,119 --> 00:09:32,679 anti-inflammatory cytokines was the down 237 00:09:37,949 --> 00:09:35,129 regulation of pro-inflammatory cytokines 238 00:09:40,739 --> 00:09:37,959 extremely important especially this guy 239 00:09:43,369 --> 00:09:40,749 which probably most of you have never 240 00:09:46,859 --> 00:09:43,379 heard of the matrix metalloproteinases 241 00:09:50,040 --> 00:09:46,869 these are collective group of enzymes 242 00:09:53,220 --> 00:09:50,050 that are implicated in a variety of 243 00:09:54,499 --> 00:09:53,230 diseases ranging and this is not being 244 00:09:57,530 --> 00:09:54,509 flippant about it 245 00:10:01,769 --> 00:09:57,540 ranging from sore throats to cancer 246 00:10:04,019 --> 00:10:01,779 these are really really dynamic proteins 247 00:10:06,210 --> 00:10:04,029 and when they are up regulated there's 248 00:10:07,619 --> 00:10:06,220 nothing but trouble the pharmaceutical 249 00:10:10,910 --> 00:10:07,629 industry over the last eight years has 250 00:10:12,499 --> 00:10:10,920 spent over six billion dollars to find 251 00:10:16,169 --> 00:10:12,509 inhibitors of 252 00:10:19,139 --> 00:10:16,179 mmp9 and MMP - they often go hand in 253 00:10:21,179 --> 00:10:19,149 hand - is not on this list because 254 00:10:22,859 --> 00:10:21,189 although we down regulated it in this 255 00:10:26,910 --> 00:10:22,869 experiment it wasn't to a statistically 256 00:10:29,369 --> 00:10:26,920 significant level the point is that we 257 00:10:31,439 --> 00:10:29,379 are simultaneously up regulating anti 258 00:10:32,819 --> 00:10:31,449 inflammatory cytokines down-regulating 259 00:10:36,059 --> 00:10:32,829 pro-inflammatory cytokines and 260 00:10:40,109 --> 00:10:36,069 down-regulating mmp-9 and we'll see what 261 00:10:42,600 --> 00:10:40,119 that means here a little while so let's 262 00:10:44,129 --> 00:10:42,610 look at some some practical applications 263 00:10:46,650 --> 00:10:44,139 of what we're finding with streptomycin 264 00:10:48,389 --> 00:10:46,660 though these four experiments are going 265 00:10:50,460 --> 00:10:48,399 to get about two minutes each these are 266 00:10:52,259 --> 00:10:50,470 all done in horses all done in with 267 00:10:54,059 --> 00:10:52,269 collaboration with investigators at the 268 00:10:55,499 --> 00:10:54,069 University of Kentucky or with 269 00:10:57,389 --> 00:10:55,509 practicing veterinarians and the large 270 00:10:59,519 --> 00:10:57,399 equine practices in the Lexington area 271 00:11:02,850 --> 00:10:59,529 all the animals are going to look at our 272 00:11:05,280 --> 00:11:02,860 extremely expensive thoroughbreds that 273 00:11:08,519 --> 00:11:05,290 have diseases for which there isn't much 274 00:11:11,249 --> 00:11:08,529 to offer first off the bat that's a 275 00:11:13,919 --> 00:11:11,259 horse's leg actually two legs of horses 276 00:11:16,199 --> 00:11:13,929 and what we're interested here is right 277 00:11:17,639 --> 00:11:16,209 here oftentimes a horse looking injured 278 00:11:24,929 --> 00:11:17,649 that 279 00:11:26,999 --> 00:11:24,939 horse limping and not being able to be 280 00:11:30,480 --> 00:11:27,009 athletic anymore is it the tendon will 281 00:11:32,759 --> 00:11:30,490 tighten up and the hoof will lose its 282 00:11:34,499 --> 00:11:32,769 normal orientation to the ground the 283 00:11:36,480 --> 00:11:34,509 horse will be unable to use that leg 284 00:11:38,189 --> 00:11:36,490 anymore it'll go down and it won't come 285 00:11:39,290 --> 00:11:38,199 back up that that'll be a horse that's 286 00:11:42,150 --> 00:11:39,300 going to be put to sleep 287 00:11:44,519 --> 00:11:42,160 what is done for therapy for this often 288 00:11:46,559 --> 00:11:44,529 times is to cut this tendon and what 289 00:11:48,150 --> 00:11:46,569 that does is release the pressure that's 290 00:11:49,889 --> 00:11:48,160 occurring as a result of the tightening 291 00:11:51,900 --> 00:11:49,899 after the injury scar tissue forms 292 00:11:54,449 --> 00:11:51,910 there's a tightening as cross linkage of 293 00:11:56,040 --> 00:11:54,459 collagen occurs if the tendon becomes 294 00:11:59,669 --> 00:11:56,050 less flexible now we're going to cut it 295 00:12:02,460 --> 00:11:59,679 that allows the hoof to regain its 296 00:12:03,600 --> 00:12:02,470 orientation a little bit better but what 297 00:12:05,249 --> 00:12:03,610 happens when you do something like that 298 00:12:10,259 --> 00:12:05,259 you actually generate scar tissue also 299 00:12:11,519 --> 00:12:10,269 and so we have a tenotomy that's the 300 00:12:15,629 --> 00:12:11,529 cutting of the tendon that's going to 301 00:12:18,689 --> 00:12:15,639 occur with this with this situation what 302 00:12:20,639 --> 00:12:18,699 we want to do is decrease or eliminate 303 00:12:21,929 --> 00:12:20,649 the scar tissue that forms after the 304 00:12:25,139 --> 00:12:21,939 tenotomy and we're going to do that 305 00:12:27,809 --> 00:12:25,149 using slo which we find alters the ratio 306 00:12:30,150 --> 00:12:27,819 of collagen to collagenase collagenous 307 00:12:32,429 --> 00:12:30,160 breaks down collagenase breaks down 308 00:12:34,410 --> 00:12:32,439 collagen allows it to be replaced by 309 00:12:35,429 --> 00:12:34,420 more vital tissue and here's what we 310 00:12:37,379 --> 00:12:35,439 have and we're certainly not going to go 311 00:12:39,299 --> 00:12:37,389 through all this stuff except look at 312 00:12:42,480 --> 00:12:39,309 the pretty colors what we're after in 313 00:12:45,210 --> 00:12:42,490 this is we would like to see the dark 314 00:12:48,119 --> 00:12:45,220 the dark purple being shorter than the 315 00:12:51,119 --> 00:12:48,129 the light purple or the blue and this 316 00:12:53,100 --> 00:12:51,129 looks at post versus pre and what we're 317 00:12:55,350 --> 00:12:53,110 doing here is sonography where we're 318 00:12:57,389 --> 00:12:55,360 using a sonogram on the area of where 319 00:12:59,309 --> 00:12:57,399 the tenotomy is done so we get quite 320 00:13:01,259 --> 00:12:59,319 objective measurements of the amount of 321 00:13:02,910 --> 00:13:01,269 scar tissue by looking at three 322 00:13:04,590 --> 00:13:02,920 dimensional cross-sections of the tissue 323 00:13:07,199 --> 00:13:04,600 it all comes out that is the 324 00:13:09,960 --> 00:13:07,209 measurements come out of the computer so 325 00:13:13,499 --> 00:13:09,970 again its objective and what we want to 326 00:13:17,489 --> 00:13:13,509 have is smaller cross-sectional areas in 327 00:13:18,809 --> 00:13:17,499 the post this color versus the pre here 328 00:13:20,730 --> 00:13:18,819 looks pretty good this is after 30 days 329 00:13:23,369 --> 00:13:20,740 treatment that looks pretty good that's 330 00:13:25,139 --> 00:13:23,379 a turkey that's exactly wrong what went 331 00:13:27,569 --> 00:13:25,149 wrong dumb horse stepped in a hole 332 00:13:31,170 --> 00:13:27,579 during the four weeks of therapy and 333 00:13:33,810 --> 00:13:31,180 re-injured itself that's the way it goes 334 00:13:36,060 --> 00:13:33,820 this is a kind of a fun one in that you 335 00:13:37,920 --> 00:13:36,070 can see we're gaining a lot here we're 336 00:13:40,110 --> 00:13:37,930 starting to see something here after 30 337 00:13:42,720 --> 00:13:40,120 days the importance is this 338 00:13:45,870 --> 00:13:42,730 animal-headed tenotomy seven years ago 339 00:13:47,820 --> 00:13:45,880 that's an old old scar and to get any 340 00:13:50,370 --> 00:13:47,830 resolution or a hint of resolution after 341 00:13:51,810 --> 00:13:50,380 that period is something that is fairly 342 00:13:53,160 --> 00:13:51,820 unheard of and you can see the stats 343 00:13:56,100 --> 00:13:53,170 here get fifty to thirty percent 344 00:13:58,490 --> 00:13:56,110 resolution in 30 days that's a start on 345 00:14:01,410 --> 00:13:58,500 something that could be quite useful 346 00:14:02,730 --> 00:14:01,420 another problem with horses again for 347 00:14:04,740 --> 00:14:02,740 which there's little therapy especially 348 00:14:07,710 --> 00:14:04,750 in these thoroughbreds it's a problem 349 00:14:09,990 --> 00:14:07,720 our cervical adhesions these adhesions 350 00:14:13,560 --> 00:14:10,000 occur after especially multiple births 351 00:14:16,560 --> 00:14:13,570 just the act of birthing results in scar 352 00:14:18,900 --> 00:14:16,570 tissue formation and what we have here 353 00:14:20,610 --> 00:14:18,910 are eleven mares these are all 354 00:14:23,130 --> 00:14:20,620 high-price there are bred mayors that 355 00:14:26,940 --> 00:14:23,140 are barren which means that they are 356 00:14:30,000 --> 00:14:26,950 really only good for dog food anymore we 357 00:14:33,180 --> 00:14:30,010 have a an accepted these are called 358 00:14:36,410 --> 00:14:33,190 Kinney scores here we've done biopsies 359 00:14:39,390 --> 00:14:36,420 prior to SLO therapy of the cervical 360 00:14:41,370 --> 00:14:39,400 region of the horse and the Kimi scores 361 00:14:43,110 --> 00:14:41,380 go from one to three and there's a to go 362 00:14:45,180 --> 00:14:43,120 to to be you'll see in here the higher 363 00:14:47,130 --> 00:14:45,190 the number the more seriously afflicted 364 00:14:49,260 --> 00:14:47,140 the horse here we have the years which 365 00:14:51,720 --> 00:14:49,270 the mirrors have been barren here's the 366 00:14:54,720 --> 00:14:51,730 expected Foley rate or the following 367 00:14:57,270 --> 00:14:54,730 percentage 38% look at this you get 368 00:14:58,920 --> 00:14:57,280 something like number 10 has a kidney 369 00:15:00,570 --> 00:14:58,930 score of 3 that's as bad as it gets it's 370 00:15:03,780 --> 00:15:00,580 barren for a year it only has a 10% 371 00:15:07,560 --> 00:15:03,790 chance of ever having a live full okay 372 00:15:09,570 --> 00:15:07,570 this is a $500,000 mayor and she's not a 373 00:15:11,910 --> 00:15:09,580 racing mare she's a brood mare and she's 374 00:15:16,770 --> 00:15:11,920 not worth much if she can't have a foal 375 00:15:19,890 --> 00:15:16,780 so after 30 days of therapy with SLO she 376 00:15:22,020 --> 00:15:19,900 was bred the breeding was successful the 377 00:15:24,780 --> 00:15:22,030 fetus was maintained she had a live 378 00:15:27,300 --> 00:15:24,790 birth always well so bottom line is 379 00:15:29,880 --> 00:15:27,310 right down there in the corner 380 00:15:31,440 --> 00:15:29,890 we had a know just a dinky little study 381 00:15:34,470 --> 00:15:31,450 but it looks like SLO is doing something 382 00:15:36,330 --> 00:15:34,480 and remember this SLO is being 383 00:15:38,820 --> 00:15:36,340 introduced in these cases by a tiny 384 00:15:40,770 --> 00:15:38,830 injection in the neck to heal scarring 385 00:15:43,200 --> 00:15:40,780 in the uterus or in the cervix okay so 386 00:15:44,820 --> 00:15:43,210 we're getting a systemic reaction that 387 00:15:46,230 --> 00:15:44,830 way 388 00:15:48,150 --> 00:15:46,240 this is where it really gets exciting no 389 00:15:49,590 --> 00:15:48,160 this is kind of fun we're gonna look at 390 00:15:52,730 --> 00:15:49,600 a marriage uterus don't blush 391 00:15:55,400 --> 00:15:52,740 there's nothing pornographic about this 392 00:16:00,450 --> 00:15:55,410 what we're going to look at is this is a 393 00:16:03,660 --> 00:16:00,460 $750,000 mayor that had a had a Colt a 394 00:16:07,590 --> 00:16:03,670 good healthy Colt and after giving birth 395 00:16:09,240 --> 00:16:07,600 had a horrible uterine infection so as 396 00:16:11,550 --> 00:16:09,250 is typical for treating that sort of a 397 00:16:14,220 --> 00:16:11,560 case the the uterus was drenched with 398 00:16:15,540 --> 00:16:14,230 antibiotic the problem was the attending 399 00:16:17,760 --> 00:16:15,550 veterinarian didn't realize the horse 400 00:16:19,950 --> 00:16:17,770 was allergic to that antibiotic so there 401 00:16:22,650 --> 00:16:19,960 was a terrible allergic reaction 402 00:16:25,320 --> 00:16:22,660 inflammatory reaction in this uterus as 403 00:16:30,480 --> 00:16:25,330 a consequence of therapy now what we're 404 00:16:33,810 --> 00:16:30,490 going to do if I can remember how to do 405 00:16:36,180 --> 00:16:33,820 it is this we have a camera inside the 406 00:16:38,340 --> 00:16:36,190 uterus and I know this isn't the sort of 407 00:16:39,840 --> 00:16:38,350 thing you pay big bucks for but what 408 00:16:42,780 --> 00:16:39,850 we're looking at is the degree of 409 00:16:44,280 --> 00:16:42,790 scarring in this uterus and we're gonna 410 00:16:47,960 --> 00:16:44,290 see in a second this thing only lasts 411 00:16:51,210 --> 00:16:47,970 for twenty or thirty seconds look those 412 00:16:53,220 --> 00:16:51,220 those strands in there that are white 413 00:16:54,660 --> 00:16:53,230 that look some of them we'll see you 414 00:16:56,310 --> 00:16:54,670 kind of look like stalactites and 415 00:16:58,200 --> 00:16:56,320 stalagmites and they form columns that's 416 00:17:00,900 --> 00:16:58,210 all connective tissue and there's no way 417 00:17:03,720 --> 00:17:00,910 on earth that this mayor is ever going 418 00:17:07,230 --> 00:17:03,730 to be able to maintain a fetus with a 419 00:17:10,980 --> 00:17:07,240 uterus like that so we treated her with 420 00:17:12,720 --> 00:17:10,990 slo for 35 45 days she was bred 421 00:17:15,390 --> 00:17:12,730 successfully and she's had three live 422 00:17:18,449 --> 00:17:15,400 foals since that one treatment so again 423 00:17:20,550 --> 00:17:18,459 that's a that's a big deal in the horse 424 00:17:22,079 --> 00:17:20,560 industry the last thing to talk about 425 00:17:24,630 --> 00:17:22,089 horses is the last thing we want to look 426 00:17:26,630 --> 00:17:24,640 at is a recently completed study we did 427 00:17:29,670 --> 00:17:26,640 at the University of Kentucky 428 00:17:33,270 --> 00:17:29,680 Rhodococcus equi is a soil borne 429 00:17:34,320 --> 00:17:33,280 bacterium that infects young foals when 430 00:17:35,970 --> 00:17:34,330 they're out in the pasture kicking 431 00:17:37,920 --> 00:17:35,980 around and learning how to walk and 432 00:17:39,810 --> 00:17:37,930 things like that they breathe in dust 433 00:17:41,880 --> 00:17:39,820 that's contaminated with this organism 434 00:17:43,170 --> 00:17:41,890 and they get pneumonia and pneumonia can 435 00:17:48,120 --> 00:17:43,180 be fatal or it can be chronic 436 00:17:54,180 --> 00:17:48,130 what we did was artificially infect some 437 00:17:56,190 --> 00:17:54,190 foals with Rhodococcus equi and we 438 00:17:58,620 --> 00:17:56,200 divide them then into four groups those 439 00:18:01,080 --> 00:17:58,630 treated with just saline those treated 440 00:18:02,910 --> 00:18:01,090 SLO alone with the typical antibiotic 441 00:18:04,830 --> 00:18:02,920 therapy alone and the combination of 442 00:18:07,980 --> 00:18:04,840 antibiotics that's what the a B stands 443 00:18:11,490 --> 00:18:07,990 for and SLO now the reason for this is 444 00:18:12,510 --> 00:18:11,500 that in the usual route of in federal 445 00:18:14,760 --> 00:18:12,520 consequential infection the 446 00:18:15,960 --> 00:18:14,770 pathophysiology of this disease is that 447 00:18:18,270 --> 00:18:15,970 the organism gets in the lung of the 448 00:18:20,880 --> 00:18:18,280 horses it can cause immediate damage 449 00:18:22,740 --> 00:18:20,890 there to the point of fatality for the 450 00:18:24,420 --> 00:18:22,750 young foal or it can cause a chronic 451 00:18:27,030 --> 00:18:24,430 condition regardless of which it does 452 00:18:28,860 --> 00:18:27,040 well that's if there's if the foal 453 00:18:30,180 --> 00:18:28,870 survives it's going to be compromised 454 00:18:33,000 --> 00:18:30,190 the rest of its life because of a 455 00:18:34,830 --> 00:18:33,010 reduced respiratory capacity also of 456 00:18:37,860 --> 00:18:34,840 interest is that the organism becomes 457 00:18:39,540 --> 00:18:37,870 encapsulated within the lung later in 458 00:18:41,310 --> 00:18:39,550 life that capsule can breakdown live 459 00:18:43,860 --> 00:18:41,320 organisms can be spewed out underneath 460 00:18:45,750 --> 00:18:43,870 any time infection can occur again the 461 00:18:47,250 --> 00:18:45,760 reason we wanted to try slo in 462 00:18:48,600 --> 00:18:47,260 combination with the antibiotics was to 463 00:18:51,090 --> 00:18:48,610 prevent that encapsulation 464 00:18:52,680 --> 00:18:51,100 because if encapsulation occurs the 465 00:18:53,940 --> 00:18:52,690 antibiotic can never reach the organism 466 00:18:56,670 --> 00:18:53,950 so you can't kill it 467 00:18:58,920 --> 00:18:56,680 so those are the results of this little 468 00:19:00,480 --> 00:18:58,930 experiment the clinical score is a 469 00:19:02,040 --> 00:19:00,490 determination made by the attending 470 00:19:04,410 --> 00:19:02,050 veterinarian who's blinded as to which 471 00:19:07,170 --> 00:19:04,420 horse is in which of the four groups I 472 00:19:10,110 --> 00:19:07,180 mentioned and we got a p-value not bad 473 00:19:11,760 --> 00:19:10,120 of O 5 in the treated animals that is 474 00:19:13,560 --> 00:19:11,770 treated with the antibiotic process 475 00:19:16,860 --> 00:19:13,570 alone we're better off than those with 476 00:19:18,990 --> 00:19:16,870 antibiotic alone also we saw the 30 plus 477 00:19:21,440 --> 00:19:19,000 percent reduction in pneumonia scores in 478 00:19:23,700 --> 00:19:21,450 the combination another nice p-value but 479 00:19:26,190 --> 00:19:23,710 whoops wrong hand look at this guy down 480 00:19:29,280 --> 00:19:26,200 here this is really interesting here 481 00:19:30,630 --> 00:19:29,290 we're getting less collagen and that 482 00:19:32,610 --> 00:19:30,640 remember that's going to be the primary 483 00:19:35,670 --> 00:19:32,620 component in the capsulation process 484 00:19:36,870 --> 00:19:35,680 down here so that the organism that is 485 00:19:41,130 --> 00:19:36,880 causing the problem is going to be 486 00:19:45,060 --> 00:19:41,140 exposed more efficiently to the 487 00:19:47,520 --> 00:19:45,070 antibiotics and a nice p-value so what 488 00:19:50,280 --> 00:19:47,530 who cares about all these horses well we 489 00:19:53,820 --> 00:19:50,290 do in part because this is a recognized 490 00:19:55,850 --> 00:19:53,830 model for that TB in humans tuberculosis 491 00:19:57,990 --> 00:19:55,860 and humans has the same situation 492 00:19:59,580 --> 00:19:58,000 breathing the organism it can become 493 00:20:00,890 --> 00:19:59,590 encapsulated those capsules are called 494 00:20:04,440 --> 00:20:00,900 tube records you can pick them up on 495 00:20:05,400 --> 00:20:04,450 chest x-rays in this country though we 496 00:20:07,620 --> 00:20:05,410 don't get really excited about 497 00:20:10,230 --> 00:20:07,630 tuberculosis anymore there are between 498 00:20:12,169 --> 00:20:10,240 50 and 55 thousand new cases per year 499 00:20:13,820 --> 00:20:12,179 worldwide 500 00:20:16,519 --> 00:20:13,830 or not one-third of the world's 501 00:20:18,830 --> 00:20:16,529 population has tuberculosis that's a 502 00:20:21,470 --> 00:20:18,840 pretty big bunch now some of these 503 00:20:23,299 --> 00:20:21,480 people that have it are going to suffer 504 00:20:25,159 --> 00:20:23,309 the acute infection and die early on a 505 00:20:27,799 --> 00:20:25,169 lot of for a lot of people it's going to 506 00:20:30,470 --> 00:20:27,809 be a chronic infection that might become 507 00:20:31,850 --> 00:20:30,480 acute at any time as a result of 508 00:20:34,070 --> 00:20:31,860 breaking down the capsule or the 509 00:20:36,919 --> 00:20:34,080 tubercle in this case to release the 510 00:20:40,279 --> 00:20:36,929 organism we have a study planned in 511 00:20:41,450 --> 00:20:40,289 India where we will do in people that 512 00:20:44,090 --> 00:20:41,460 are afflicted with Mycobacterium 513 00:20:45,230 --> 00:20:44,100 tuberculosis the cause evasion we're 514 00:20:47,600 --> 00:20:45,240 going to do the same experiment that we 515 00:20:51,499 --> 00:20:47,610 did in the horses in Kentucky we are 516 00:20:54,499 --> 00:20:51,509 going to combine antibiotics with slo to 517 00:20:56,480 --> 00:20:54,509 see if we can break down the the capsule 518 00:20:58,310 --> 00:20:56,490 it's forming the typical expose the 519 00:20:59,239 --> 00:20:58,320 organism to the antibiotic and clear the 520 00:21:01,789 --> 00:20:59,249 people so that they're no longer 521 00:21:05,210 --> 00:21:01,799 chronically infected the importance of 522 00:21:07,999 --> 00:21:05,220 that is twofold one is typical 523 00:21:11,570 --> 00:21:08,009 antibiotic therapy for TB now lasts six 524 00:21:13,789 --> 00:21:11,580 months it's hard to keep anybody on any 525 00:21:15,859 --> 00:21:13,799 regimen for six months so people are 526 00:21:18,499 --> 00:21:15,869 going to be chronic carriers for a long 527 00:21:20,299 --> 00:21:18,509 time second thing is the longer an 528 00:21:22,639 --> 00:21:20,309 organism exposed is exposed to an 529 00:21:24,499 --> 00:21:22,649 antibiotic the greater the chance of an 530 00:21:26,899 --> 00:21:24,509 antibiotic resistant strain developing 531 00:21:29,060 --> 00:21:26,909 so what we want to do is see if we can 532 00:21:33,320 --> 00:21:29,070 reduce the clinical time of treatment 533 00:21:35,060 --> 00:21:33,330 for tuberculosis from six months to one 534 00:21:37,070 --> 00:21:35,070 or two months just doing that 535 00:21:40,070 --> 00:21:37,080 understanding that slo has no 536 00:21:41,509 --> 00:21:40,080 antimicrobial activity of its own it's 537 00:21:43,129 --> 00:21:41,519 got to be used in conjunction with the 538 00:21:46,669 --> 00:21:43,139 antibiotics but we think we might be 539 00:21:49,039 --> 00:21:46,679 able to help now we've talked about some 540 00:21:50,600 --> 00:21:49,049 internal scarring associated diseases 541 00:21:52,399 --> 00:21:50,610 with horses we looked at the legs of the 542 00:21:55,549 --> 00:21:52,409 one horse on the uterus and the cervix 543 00:21:58,609 --> 00:21:55,559 and so forth what about humans these 544 00:21:59,989 --> 00:21:58,619 first four dot points represent some of 545 00:22:03,289 --> 00:21:59,999 the diseases we've treated successfully 546 00:22:06,350 --> 00:22:03,299 using slo these are all sky related 547 00:22:08,090 --> 00:22:06,360 diseases cardiomyopathy horrible disease 548 00:22:10,310 --> 00:22:08,100 we've had a couple patients that were on 549 00:22:12,529 --> 00:22:10,320 the cardiac transplant list that are no 550 00:22:14,899 --> 00:22:12,539 longer on it so that's that's a good 551 00:22:17,060 --> 00:22:14,909 sign polycystic kidney disease no 552 00:22:18,649 --> 00:22:17,070 responds quickly surgical adhesions are 553 00:22:21,139 --> 00:22:18,659 a big problem especially with gut 554 00:22:23,090 --> 00:22:21,149 surgery or gynecological surgery we can 555 00:22:25,220 --> 00:22:23,100 make those surgical adhesions pretty 556 00:22:28,670 --> 00:22:25,230 much disappear 557 00:22:31,160 --> 00:22:28,680 the range of motion for all of us 558 00:22:34,100 --> 00:22:31,170 decreases with age in part because of 559 00:22:35,690 --> 00:22:34,110 adhesions and we have little study 560 00:22:37,070 --> 00:22:35,700 actually a pretty good size study ready 561 00:22:38,780 --> 00:22:37,080 to start later this year at Yale 562 00:22:40,310 --> 00:22:38,790 University Medical School where we will 563 00:22:42,260 --> 00:22:40,320 treat patients with complications of 564 00:22:43,700 --> 00:22:42,270 total knee replacement surgery because 565 00:22:45,350 --> 00:22:43,710 anecdotally we've seen these patients 566 00:22:48,410 --> 00:22:45,360 get a heck of a lot better with slo 567 00:22:50,060 --> 00:22:48,420 therapy we are just now starting to put 568 00:22:52,180 --> 00:22:50,070 our foot in the water with respect to 569 00:22:54,590 --> 00:22:52,190 treating concussions 570 00:22:55,850 --> 00:22:54,600 we're not scarring in the brain is a 571 00:22:57,320 --> 00:22:55,860 little bit different than it then 572 00:22:58,550 --> 00:22:57,330 scarring elsewhere in the body we're not 573 00:23:00,800 --> 00:22:58,560 sure what will happen here but we're 574 00:23:03,650 --> 00:23:00,810 working with two groups on this project 575 00:23:05,500 --> 00:23:03,660 this proposed project one is the with 576 00:23:07,880 --> 00:23:05,510 the people at the Medical School in 577 00:23:09,560 --> 00:23:07,890 Johnson City Tennessee eastern Tennessee 578 00:23:11,930 --> 00:23:09,570 Medical School the other group is called 579 00:23:14,570 --> 00:23:11,940 the National Football League and we're 580 00:23:19,750 --> 00:23:14,580 going to see if if SLO can do anything 581 00:23:25,100 --> 00:23:23,180 we've talked a little bit about external 582 00:23:26,720 --> 00:23:25,110 scars in humans one of the first 583 00:23:29,840 --> 00:23:26,730 patients was well maybe I didn't tell 584 00:23:31,790 --> 00:23:29,850 you about that I told you about the gal 585 00:23:33,920 --> 00:23:31,800 that tried to punch out to the physician 586 00:23:37,340 --> 00:23:33,930 one of the other patients we brought in 587 00:23:41,170 --> 00:23:37,350 was a man in his in his mid-70s 75 76 588 00:23:44,600 --> 00:23:41,180 years old who had acne scars since since 589 00:23:47,450 --> 00:23:44,610 his teenage years and in four weeks 590 00:23:49,820 --> 00:23:47,460 those flattened out okay so this this is 591 00:23:51,320 --> 00:23:49,830 a hint of another use for this and prom 592 00:23:56,030 --> 00:23:51,330 and do scars stretch marks and all that 593 00:24:00,430 --> 00:23:56,040 that's great what about if we used slo 594 00:24:04,370 --> 00:24:00,440 to prevent scars rather than to just 595 00:24:06,200 --> 00:24:04,380 treat them well this is a picture of a 596 00:24:06,770 --> 00:24:06,210 gals face just after she went through a 597 00:24:10,220 --> 00:24:06,780 windshield 598 00:24:12,290 --> 00:24:10,230 there's her chin here's her teeth her 599 00:24:16,070 --> 00:24:12,300 nose has been torn off and displaced to 600 00:24:17,780 --> 00:24:16,080 the right she's in trouble at the time 601 00:24:19,340 --> 00:24:17,790 of the picture she's at the emergency 602 00:24:23,720 --> 00:24:19,350 room at the Medical University of South 603 00:24:24,830 --> 00:24:23,730 Carolina she's getting sewed up here you 604 00:24:26,660 --> 00:24:24,840 can see there gonna be a problem with 605 00:24:28,640 --> 00:24:26,670 the scar here look at the position this 606 00:24:29,360 --> 00:24:28,650 tube the right side of her mouth has 607 00:24:31,850 --> 00:24:29,370 been ripped out 608 00:24:33,830 --> 00:24:31,860 they got her nose back on now but there 609 00:24:36,200 --> 00:24:33,840 gonna be some scarring there some scar 610 00:24:38,270 --> 00:24:36,210 over the eyes and so forth her mother is 611 00:24:39,020 --> 00:24:38,280 a nurse and one of the practices that's 612 00:24:41,540 --> 00:24:39,030 in our group 613 00:24:43,310 --> 00:24:41,550 when she got the call from the from the 614 00:24:44,570 --> 00:24:43,320 medical school saying that her daughter 615 00:24:46,040 --> 00:24:44,580 had been the accident she ran out the 616 00:24:49,760 --> 00:24:46,050 door and said can I take some SLO with 617 00:24:52,430 --> 00:24:49,770 me and of course she did and this 618 00:24:54,560 --> 00:24:52,440 patient then started SLO again just a 619 00:24:57,890 --> 00:24:54,570 drop under the tongue four times a day 620 00:25:01,280 --> 00:24:57,900 the day of her accident whoops wrong 621 00:25:02,540 --> 00:25:01,290 button here she is looking pretty great 622 00:25:04,520 --> 00:25:02,550 don't you think it looks like she might 623 00:25:07,550 --> 00:25:04,530 have a scar on her left cheek they're 624 00:25:08,120 --> 00:25:07,560 gonna get a scar on her nose she's in 625 00:25:12,170 --> 00:25:08,130 trouble 626 00:25:15,260 --> 00:25:12,180 there she is three weeks later and if 627 00:25:16,430 --> 00:25:15,270 you look she still has a scar something 628 00:25:17,630 --> 00:25:16,440 that by the way all these pictures are 629 00:25:20,630 --> 00:25:17,640 taken by her mother who's not a 630 00:25:23,270 --> 00:25:20,640 professional photographer there she is 631 00:25:25,340 --> 00:25:23,280 a month after after the last picture 632 00:25:26,690 --> 00:25:25,350 again that scar is still flattening out 633 00:25:28,430 --> 00:25:26,700 it's got a ways to go yet but that's not 634 00:25:30,470 --> 00:25:28,440 too bad you don't see much around the 635 00:25:33,950 --> 00:25:30,480 nose at all look at that that's coming 636 00:25:36,320 --> 00:25:33,960 right along this is a this is a step in 637 00:25:39,350 --> 00:25:36,330 the right direction now the physicians 638 00:25:41,180 --> 00:25:39,360 in our group use SLO routinely for 639 00:25:44,090 --> 00:25:41,190 patients before they go into therapy and 640 00:25:47,150 --> 00:25:44,100 what we have found is the patients heal 641 00:25:48,620 --> 00:25:47,160 with little or no scarring after I say 642 00:25:50,270 --> 00:25:48,630 after therapy after surgery before they 643 00:25:52,700 --> 00:25:50,280 go into surgery they're healing with 644 00:25:56,750 --> 00:25:52,710 little or no scarring they don't need as 645 00:25:58,580 --> 00:25:56,760 much analgesia after surgery and again 646 00:25:59,750 --> 00:25:58,590 we know some reason about that we saw 647 00:26:02,090 --> 00:25:59,760 the up regulation of the 648 00:26:04,550 --> 00:26:02,100 anti-inflammatory down regulation of 649 00:26:05,450 --> 00:26:04,560 pro-inflammatory cytokines and they heal 650 00:26:10,580 --> 00:26:05,460 much quicker and they hear without 651 00:26:12,530 --> 00:26:10,590 adhesions now now let's go back to this 652 00:26:14,180 --> 00:26:12,540 young lady for a second so I can 653 00:26:15,800 --> 00:26:14,190 introduce you that next slide this is 654 00:26:17,600 --> 00:26:15,810 all great stuff hooray you know great we 655 00:26:18,950 --> 00:26:17,610 can do something with scars but it still 656 00:26:22,550 --> 00:26:18,960 doesn't get to the point that we were 657 00:26:25,340 --> 00:26:22,560 asking at the very start of this tirade 658 00:26:27,080 --> 00:26:25,350 that I'm giving you that was we've 659 00:26:29,120 --> 00:26:27,090 mentioned that this platform the 660 00:26:31,640 --> 00:26:29,130 resident molecular signaling platform 661 00:26:33,260 --> 00:26:31,650 that we've developed is making an 662 00:26:35,600 --> 00:26:33,270 assumption that the therapeutic agents 663 00:26:38,300 --> 00:26:35,610 that we use are simply acting as signals 664 00:26:40,580 --> 00:26:38,310 and again if you can use the same 665 00:26:43,340 --> 00:26:40,590 product for a 2,000 pound horse as a you 666 00:26:44,570 --> 00:26:43,350 know as a cat and which we do good it 667 00:26:46,430 --> 00:26:44,580 works just like that 668 00:26:48,320 --> 00:26:46,440 it works super but what's the nature of 669 00:26:50,390 --> 00:26:48,330 the signal well we're not smart enough 670 00:26:52,730 --> 00:26:50,400 to figure it out ourselves so we asked 671 00:26:54,230 --> 00:26:52,740 the help of the personnel 672 00:26:56,419 --> 00:26:54,240 what's called the center for cell 673 00:26:57,710 --> 00:26:56,429 signaling at the medical medical school 674 00:27:00,230 --> 00:26:57,720 at the University of Virginia 675 00:27:02,720 --> 00:27:00,240 David Brautigan is the director of that 676 00:27:04,669 --> 00:27:02,730 program down there we got in touch with 677 00:27:06,380 --> 00:27:04,679 him send him some of the data and a 678 00:27:08,690 --> 00:27:06,390 whole lot more some of the data you've 679 00:27:11,240 --> 00:27:08,700 seen here and an awful lot more and said 680 00:27:13,159 --> 00:27:11,250 can you help us figure out what's going 681 00:27:14,389 --> 00:27:13,169 on here he looked at all the data he 682 00:27:16,669 --> 00:27:14,399 says I've never seen anything like it 683 00:27:18,440 --> 00:27:16,679 and this is the guy that's director of 684 00:27:20,720 --> 00:27:18,450 cell signaling say well can you help us 685 00:27:22,450 --> 00:27:20,730 anyway he said let's do this we've got 686 00:27:24,440 --> 00:27:22,460 some in vitro assays we do a lot of 687 00:27:26,029 --> 00:27:24,450 cancer work down here at University of 688 00:27:28,370 --> 00:27:26,039 Virginia we have some in vitro assays 689 00:27:30,320 --> 00:27:28,380 you'll recall one of the slides way back 690 00:27:34,070 --> 00:27:30,330 showed down-regulation of 691 00:27:35,840 --> 00:27:34,080 mmp9 that's one of the markers that's 692 00:27:38,180 --> 00:27:35,850 associated with cancer he said let's 693 00:27:41,090 --> 00:27:38,190 take a look since you've got this this 694 00:27:42,799 --> 00:27:41,100 date about mmp9 let's see if SLO does 695 00:27:44,269 --> 00:27:42,809 anything in one of our in vitro assays 696 00:27:46,639 --> 00:27:44,279 then that'll give us a handle on where 697 00:27:50,269 --> 00:27:46,649 to go next so now we get to look at this 698 00:27:51,350 --> 00:27:50,279 slide what we have here whoops in the in 699 00:27:52,190 --> 00:27:51,360 the top four little pictures are 700 00:27:56,690 --> 00:27:52,200 photomicrographs 701 00:28:00,830 --> 00:27:56,700 of cells that have passed through a gel 702 00:28:03,529 --> 00:28:00,840 matrix that that reflects the ability of 703 00:28:07,669 --> 00:28:03,539 those cells to metastasize in the human 704 00:28:11,210 --> 00:28:07,679 body these cells are of human breast 705 00:28:13,549 --> 00:28:11,220 cancer origin they are them the most 706 00:28:16,310 --> 00:28:13,559 aggressive form of breast cancer in 707 00:28:18,560 --> 00:28:16,320 humans okay now look all we're doing 708 00:28:19,820 --> 00:28:18,570 without getting into too much detail is 709 00:28:20,960 --> 00:28:19,830 counting the number of cells that have 710 00:28:22,789 --> 00:28:20,970 made it through the matrix that's an 711 00:28:25,010 --> 00:28:22,799 indication of their degree of metastatic 712 00:28:27,380 --> 00:28:25,020 ability okay and you look at different 713 00:28:29,269 --> 00:28:27,390 concentrations of slo and you have 714 00:28:32,480 --> 00:28:29,279 progressively fewer cells making it 715 00:28:34,250 --> 00:28:32,490 through these bar graphs simply show in 716 00:28:36,970 --> 00:28:34,260 in this one what we're seeing in these 717 00:28:40,430 --> 00:28:36,980 pictures okay and each one of these is 718 00:28:42,350 --> 00:28:40,440 statistically significant so now we have 719 00:28:43,610 --> 00:28:42,360 a product that not only does something 720 00:28:44,419 --> 00:28:43,620 with scars that looks like it emits 721 00:28:47,600 --> 00:28:44,429 metastases 722 00:28:49,399 --> 00:28:47,610 when dr. Brautigan uva saw this the 723 00:28:52,639 --> 00:28:49,409 first thing he said was every woman over 724 00:28:54,830 --> 00:28:52,649 40 should be taking us hello that that's 725 00:28:56,779 --> 00:28:54,840 and this this is the guy that works with 726 00:29:00,169 --> 00:28:56,789 cancer all the time well maybe yes maybe 727 00:29:01,730 --> 00:29:00,179 no the point of it is that we are now in 728 00:29:04,899 --> 00:29:01,740 our laboratories and Providence Rhode 729 00:29:06,180 --> 00:29:04,909 Island doing some work to see if what 730 00:29:08,700 --> 00:29:06,190 brought 731 00:29:12,180 --> 00:29:08,710 saw in vitro in Virginia can reproduce 732 00:29:13,980 --> 00:29:12,190 can be reproduced in vivo will we really 733 00:29:20,070 --> 00:29:13,990 show that decrease in metastatic 734 00:29:22,409 --> 00:29:20,080 activity to round us all up resident 735 00:29:25,110 --> 00:29:22,419 molecular signaling is the platform that 736 00:29:27,419 --> 00:29:25,120 we've developed I'm confident that all 737 00:29:29,190 --> 00:29:27,429 we're doing is bridging biochemistry and 738 00:29:32,070 --> 00:29:29,200 biophysics we can explain everything we 739 00:29:32,639 --> 00:29:32,080 see biochemically but that's not the 740 00:29:34,980 --> 00:29:32,649 right answer 741 00:29:37,740 --> 00:29:34,990 there's more going at a different level 742 00:29:39,690 --> 00:29:37,750 which I'm calling biophysics and that 743 00:29:42,659 --> 00:29:39,700 gets us to this question of what's the 744 00:29:44,430 --> 00:29:42,669 nature of the signal the reason we're 745 00:29:46,440 --> 00:29:44,440 asking that question is not for academic 746 00:29:47,970 --> 00:29:46,450 purposes but we think that other 747 00:29:49,499 --> 00:29:47,980 modalities might be identified that 748 00:29:52,619 --> 00:29:49,509 could be more efficient than what we're 749 00:29:55,320 --> 00:29:52,629 doing maybe sound might be light mic the 750 00:29:57,029 --> 00:29:55,330 electromagnetic force any of those I 751 00:29:58,799 --> 00:29:57,039 have in parentheses bone healing they're 752 00:30:00,629 --> 00:29:58,809 just as kind of an aside to tell you 753 00:30:02,340 --> 00:30:00,639 that you all know that you can use 754 00:30:04,200 --> 00:30:02,350 magnets to stimulate bone healing right 755 00:30:05,940 --> 00:30:04,210 that's been in the literature hospitals 756 00:30:06,749 --> 00:30:05,950 use that all the time now we have a 757 00:30:08,759 --> 00:30:06,759 molecule 758 00:30:11,940 --> 00:30:08,769 it's called calmodulin that stimulates 759 00:30:14,820 --> 00:30:11,950 bone healing faster than magnet what's 760 00:30:18,299 --> 00:30:14,830 the common denominator between the 761 00:30:21,240 --> 00:30:18,309 calmodulin the biochemical approach and 762 00:30:22,139 --> 00:30:21,250 the magnet the biophysical we don't know 763 00:30:25,259 --> 00:30:22,149 we need help 764 00:30:32,490 --> 00:30:25,269 that's why I'm here and for that I thank 765 00:30:37,090 --> 00:30:34,810 looking for questions I imagine they'll 766 00:30:39,100 --> 00:30:37,100 be one or two I have to tell you that 767 00:30:42,100 --> 00:30:39,110 I've spoken at John's annual conference 768 00:30:44,649 --> 00:30:42,110 of his Beechtree labs and it's a mini 769 00:30:45,370 --> 00:30:44,659 version of sse then he calls the members 770 00:30:52,120 --> 00:30:45,380 beechnuts 771 00:30:56,169 --> 00:30:52,130 yeah thank you war that was really 772 00:31:00,279 --> 00:30:56,179 inspiring I understand that one of the 773 00:31:03,250 --> 00:31:00,289 reasons why spinal cord injuries after a 774 00:31:05,590 --> 00:31:03,260 period of time you know cannot be healed 775 00:31:07,299 --> 00:31:05,600 is because of scar tissue is there a 776 00:31:08,710 --> 00:31:07,309 possibility that this will work well 777 00:31:11,259 --> 00:31:08,720 that kind of thing if applied 778 00:31:15,370 --> 00:31:11,269 immediately after an injury it does work 779 00:31:17,289 --> 00:31:15,380 we've done it one of the Articles that I 780 00:31:19,539 --> 00:31:17,299 make my students undergraduate students 781 00:31:21,730 --> 00:31:19,549 read is as an article on use of stem 782 00:31:25,299 --> 00:31:21,740 cells and in that very injury in horses 783 00:31:27,930 --> 00:31:25,309 and it reported that there was very good 784 00:31:31,090 --> 00:31:27,940 good results from it have you looked at 785 00:31:33,720 --> 00:31:31,100 the comparison with the use of stem 786 00:31:36,970 --> 00:31:33,730 cells or using stem cells in in 787 00:31:38,409 --> 00:31:36,980 connection with slo we've not done any 788 00:31:39,610 --> 00:31:38,419 comparative work other than through the 789 00:31:40,930 --> 00:31:39,620 experiences of the attending 790 00:31:42,310 --> 00:31:40,940 veterinarians that are come from some of 791 00:31:46,629 --> 00:31:42,320 these really big clinics in the 792 00:31:48,700 --> 00:31:46,639 Lexington area and they're from their 793 00:31:52,210 --> 00:31:48,710 experiences their observations the 794 00:31:53,649 --> 00:31:52,220 results are pretty much similar the they 795 00:31:58,480 --> 00:31:53,659 like the SLO because it's easier and 796 00:32:00,310 --> 00:31:58,490 cheaper John I'm wondering if you've 797 00:32:02,889 --> 00:32:00,320 tried you mentioned horses I'm wondering 798 00:32:04,810 --> 00:32:02,899 if you have tried anything with dairy 799 00:32:06,879 --> 00:32:04,820 cattle in particular mastitis or bangs 800 00:32:11,019 --> 00:32:06,889 disease you know nothing with bangs lots 801 00:32:12,759 --> 00:32:11,029 with staph aureus induced mastitis and I 802 00:32:14,259 --> 00:32:12,769 would say our success has been limited 803 00:32:17,649 --> 00:32:14,269 primarily because the farmers don't want 804 00:32:19,240 --> 00:32:17,659 to keep up the therapy but we have had 805 00:32:20,680 --> 00:32:19,250 some degree of success we have not done 806 00:32:22,240 --> 00:32:20,690 a real trial with it we have 807 00:32:24,399 --> 00:32:22,250 veterinarians in our group who do use it 808 00:32:26,250 --> 00:32:24,409 routinely and finally I think I can help 809 00:32:29,759 --> 00:32:26,260 you get some of your answers I 810 00:32:31,810 --> 00:32:29,769 appreciate it thank you I'm just on 811 00:32:35,379 --> 00:32:31,820 theory behind all this have you ever 812 00:32:39,279 --> 00:32:35,389 encountered papers on non-contact 813 00:32:40,870 --> 00:32:39,289 friction no sound familiar you know this 814 00:32:42,970 --> 00:32:40,880 I think this you're on the bottom floor 815 00:32:44,350 --> 00:32:42,980 of a whole field of science that any 816 00:32:46,930 --> 00:32:44,360 animal molecule 817 00:32:49,570 --> 00:32:46,940 has a intense virtual photon field 818 00:32:51,280 --> 00:32:49,580 around it that's sort of like not not 819 00:32:53,830 --> 00:32:51,290 recognised by physics was just starting 820 00:32:56,370 --> 00:32:53,840 to to become that and that non-contact 821 00:32:59,110 --> 00:32:56,380 friction is that separate molecules 822 00:33:01,870 --> 00:32:59,120 hundred animals apart in nanometers 823 00:33:04,780 --> 00:33:01,880 apart have very strong friction between 824 00:33:06,760 --> 00:33:04,790 them for like AFM microscope stuff I 825 00:33:09,100 --> 00:33:06,770 would love to be introduced to it but 826 00:33:12,760 --> 00:33:09,110 look up non-contact friction will do it 827 00:33:13,560 --> 00:33:12,770 thank you I have a question and a 828 00:33:17,250 --> 00:33:13,570 comment 829 00:33:20,650 --> 00:33:17,260 I'm I'm interested in the dose response 830 00:33:22,180 --> 00:33:20,660 efficacy because if this is a molecular 831 00:33:24,940 --> 00:33:22,190 signaling kind of effect you might 832 00:33:27,820 --> 00:33:24,950 expect it to be those independent but I 833 00:33:31,510 --> 00:33:27,830 saw your dose response curve and in the 834 00:33:34,360 --> 00:33:31,520 last graph kind of indicating that it's 835 00:33:36,039 --> 00:33:34,370 acting like a ordinary biochemical kind 836 00:33:38,830 --> 00:33:36,049 of that's the first time we've ever seen 837 00:33:41,830 --> 00:33:38,840 anything like that so that's alone so 838 00:33:43,030 --> 00:33:41,840 nonetheless I wonder if you had done any 839 00:33:47,320 --> 00:33:43,040 experiments going the other direction 840 00:33:48,970 --> 00:33:47,330 like toward the ultra low light oceans 841 00:33:51,370 --> 00:33:48,980 we've done lots of that with the idea of 842 00:33:53,890 --> 00:33:51,380 hormesis involved yes right absolutely 843 00:33:55,960 --> 00:33:53,900 we have and it works at ultra low doses 844 00:33:57,909 --> 00:33:55,970 actually these are these are relatively 845 00:33:59,440 --> 00:33:57,919 ultra low doses and we get the classic 846 00:34:01,659 --> 00:33:59,450 u-shaped or J shaped curve that's 847 00:34:03,039 --> 00:34:01,669 associated with hormesis and these doses 848 00:34:05,620 --> 00:34:03,049 that I'm talking about are at the bottom 849 00:34:07,990 --> 00:34:05,630 of that you okay okay so that's they are 850 00:34:10,240 --> 00:34:08,000 it a higher dose clinically a higher 851 00:34:11,790 --> 00:34:10,250 dose will give us no response and a 852 00:34:14,169 --> 00:34:11,800 lower dose will give us no response 853 00:34:16,570 --> 00:34:14,179 there is a window with that new shape 854 00:34:19,060 --> 00:34:16,580 okay so that's encouraging and as far as 855 00:34:21,340 --> 00:34:19,070 testing hypothesis that there's some 856 00:34:23,349 --> 00:34:21,350 endogenous electromagnetic field which 857 00:34:27,099 --> 00:34:23,359 might carry the information like my 858 00:34:29,710 --> 00:34:27,109 laser last night I you could do 859 00:34:31,780 --> 00:34:29,720 experiments with looking for synergism 860 00:34:34,300 --> 00:34:31,790 between the chemical and an 861 00:34:36,450 --> 00:34:34,310 electromagnet exogenous electromagnetic 862 00:34:38,649 --> 00:34:36,460 field to see if there's any coupling or 863 00:34:39,909 --> 00:34:38,659 synergism between the two that's where 864 00:34:43,690 --> 00:34:39,919 we need help because we're too dumb to 865 00:34:47,560 --> 00:34:43,700 do those sorts of experiments Thank You 866 00:34:56,350 --> 00:34:53,830 bill didn't see you behind me thanks 867 00:34:59,590 --> 00:34:56,360 John I was wondering if you also have 868 00:35:02,440 --> 00:34:59,600 looked for a dose-response curve the 869 00:35:05,590 --> 00:35:02,450 u-shaped thing with respect to the 870 00:35:11,650 --> 00:35:05,600 frequency of repetition of the dose yes 871 00:35:13,750 --> 00:35:11,660 and it's interesting you ask the we can 872 00:35:16,510 --> 00:35:13,760 use a light switch as an example of what 873 00:35:17,950 --> 00:35:16,520 happens and all that you can you can 874 00:35:19,000 --> 00:35:17,960 turn a light switch on gently or can 875 00:35:20,980 --> 00:35:19,010 smash the heck out of it but you don't 876 00:35:23,620 --> 00:35:20,990 get any different response right either 877 00:35:28,630 --> 00:35:23,630 turns on or it doesn't what we find is 878 00:35:32,950 --> 00:35:28,640 that especially in acute diseases if we 879 00:35:35,620 --> 00:35:32,960 in a sense pulse therapy we get a better 880 00:35:37,000 --> 00:35:35,630 result early on and then we can reduce 881 00:35:38,680 --> 00:35:37,010 the frequency of administration but we 882 00:35:41,470 --> 00:35:38,690 keep the dose the same so it's like 883 00:35:43,170 --> 00:35:41,480 flicking the light switch on and off we 884 00:35:47,140 --> 00:35:43,180 think it's more important to have 885 00:35:51,880 --> 00:35:47,150 multiple endpoints in inputs than one 886 00:35:53,350 --> 00:35:51,890 big one and so yes and for example with 887 00:35:56,020 --> 00:35:53,360 rheumatoid arthritis we have a 888 00:35:57,340 --> 00:35:56,030 formulation that we use for that person 889 00:35:59,290 --> 00:35:57,350 is an extreme pain they're still going 890 00:36:01,690 --> 00:35:59,300 to take sublingual drops we would ask 891 00:36:03,670 --> 00:36:01,700 them to take a sublingual drop every 15 892 00:36:06,160 --> 00:36:03,680 minutes for an hour users in the hour 893 00:36:07,750 --> 00:36:06,170 that pain starts to resolve after they 894 00:36:10,480 --> 00:36:07,760 get over that threshold where pain 895 00:36:12,370 --> 00:36:10,490 reduction has begun they can decrease 896 00:36:15,460 --> 00:36:12,380 the frequency of drop maintain the same 897 00:36:17,500 --> 00:36:15,470 concentration and they'll be fine if 898 00:36:19,300 --> 00:36:17,510 they don't decrease the frequency 899 00:36:21,550 --> 00:36:19,310 it won't hurt them anything just wasted 900 00:36:22,930 --> 00:36:21,560 drops oh sorry it's just wasted drops 901 00:36:26,130 --> 00:36:22,940 you know it doesn't hurt them any so it 902 00:36:29,010 --> 00:36:26,140 doesn't doesn't overdose them okay nope