The dominant diseases of modernized societies as omega-3 essential fatty acid deficiency syndrome: Substrate beriberi

About 1900, modern food selection and processing caused widespread $\text{epidemics}$ of the B vitamin deficiency diseases of beriberi and pellagra which, for genetic reasons, often expressed as different diseases ranging from bowel and heart disease to dermatoses and psychoses. But the B vitamins merely help convert essential fatty acids (EFA) into the prostaglandin (PG) tissue regulators and it now turns out that, through hydrogenation, milling and selection of w3-poor southern foods, we have also been systematically depleting, by as much as 90%, a newly discovered trace Nordic EFA (w3) of special importance to primates and sole precursor of the PG3(4) series, even as a concurrent fiber deficiency increases body demand for EFA. Since substrate EFA is processed by many B vitamin catalysts, an EFA deficiency will mimic a $\text{panh}$ypovitaminosis B, i.e., a mixture of $\text{substrate}$ beriberi and $\text{substrate}$ pellagra resembling vitamin beriberi and pellagra but exhibiting as even more diverse $\text{endemic}$ disease. This would consitute a second stage of the Modern Malnutrition and explain why some workers now hold the dominant diseases of modermized societies to be new, nutritionally based, pellagraform yet lipid-related and to range, once again, from heart disease to psychosis. It is an assumption that our dominant diseases are unrelated to each other or are merely revealed by our diagnostic acumen and therapeutic success; and that hydrogenating millions of tons of food oils annually, to destroy the rancidity producing w3-EFA, is safe for $\text{primates}$. Extensive beriberiform disease is reported here in 32 typical cases taken from medical practice which responds strikingly to linseed oil supplements (60% w3-EFA) in confirmation of identical results in Capuchins.     

Nandrolone decanoate has long-term effects on dominance in a competitive situation in male rats

The aim of the present study was to examine possible long-term effects of the anabolic androgenic steroid (AAS), nandrolone decanoate (ND), on dominance in a provoking and competitive situation in sexually matured male rats. The experimental group (n=10) received daily injections of ND [15 mg/kg in a volume of 1 ml/kg subcutaneous (s.c.) injection for 14 days]. During the corresponding period, the controls (n=10) were given daily injections of an oil vehicle (1 ml/kg s.c.). All animals were tested in a competitive situation at four occasions after the end of the treatment period (week 5, 8, 11 and 14). Water-deprived pairs of rats, consisting of one ND-treated rat and one control, had to compete for access to water. The results showed that the ND-treated rats approached the water spout significantly more often compared to the controls. During the competition tests, the ND-treated rats spent more time drinking, an effect that was prominent for 11 weeks after the end of the treatment period. The ND-treated rats also displayed more frequently piloerection than the controls. The results indicate that ND has long-term effect on dominance in a provoking and competitive situation.     

Androgenetic alopecia in children: report of 20 cases

Androgenetic alopecia (AGA) is the most common type of hair loss in adults. Although there are differences in the age at onset, the disease starts after puberty when enough testosterone is available to be transformed into dihydrotestosterone. We report 20 prepubertal children with AGA, 12 girls and eight boys, age range 6-10 years, observed over the last 4 years. All had normal physical development. Clinical examination showed hair loss with thinning and widening of the central parting of the scalp, both in boys and girls. In eight cases frontal accentuation and breach of frontal hairline were also present. The clinical diagnosis was confirmed by pull test, trichogram and dermoscopy in all cases, and by scalp biopsy performed in six cases. There was a strong family history of AGA in all patients. The onset of AGA is not expected to be seen in prepubertal patients without abnormal androgen levels. A common feature observed in our series of children with AGA was a strong genetic predisposition to the disease. Although the pathogenesis remains speculative, endocrine evaluation and a strict follow-up are strongly recommended.     

Identification of differentially expressed genes in anagen dermal papilla by suppression subtractive hybridization

Background We constructed a cDNA subtractive library of dermal papilla cells (DPCs) in anagen with suppression subtractive hybridization (SSH) technique and clone differentially expressed genes related to DPCs in anagen. Methods Total mRNA was isolated from DPCs of anagen and telogen follicles. Moreover, singlestrand (ss) and double-strand (ds) cDNAs were synthesized in turn using SMART PCR cDNA synthesis technology, ds cDNAs then were digested with Rsa I and divided into two groups, and ligated to the specific adaptor 1 and adaptor 2R, respectively. After cDNAs were hybridized with each other twice and underwent two rounds of nested PCR. PCR products were ligated with arms of T/A plasmid vectors to set up the subtractive library. Selected clones were demonstrated by reverse Northern blot and sequenced. The acquired sequence data were aligned against the Genbank nucleotide database. Results cDNA subtractive library of DPCs in anagen follicles was set up successfully with high subtractive efficiency, Thirty-five genes were identified in this study with 22 known functional genesand 13 unknown functional genes. Conclusions All results confirm the effectiveness and sensitivity of SSH in detecting differentially expressed genes from a small amount of clinical samples. Information about such alterations in gene expression could be useful for elucidating the genetic events in hair follicle growth regulation.     

Lack of evidence for opioid tolerance or dependence in rhesus monkeys following high-dose anabolic-androgenic steroid administration

Prolonged use of high-dose anabolic–androgenic steroids (AAS) may induce a dependence syndrome, and emerging evidence suggests that AAS effects on endogenous opioid systems may contribute to AAS abuse. The present study tested the hypothesis that high dose AAS treatment enhances endogenous opioid activity in rhesus monkeys as revealed by 1) tolerance to the antinociceptive effects of the mu opioid agonist morphine and 2) physical dependence as indicated by evidence of opioid withdrawal following administration of the opioid antagonist naloxone. Three rhesus monkeys were treated for 14 days with 3.2 mg/kg/day testosterone propionate, and the effects of morphine (0.32–10 mg/kg) and naloxone (0.01–0.32 mg/kg) were examined both before and during treatment. Morphine antinociception was evaluated using a warm-water tail-withdrawal procedure, and naloxone-precipitated withdrawal was evaluated using checked behavioral signs and measures of ventilatory rate. Chronic testosterone administration for 14 days produced a 100-fold increase in mean plasma testosterone levels. However, testosterone treatment did not significantly alter the antinociceptive effects of morphine, and naloxone did not precipitate signs of opioid withdrawal either before or during testosterone treatment. These data do not support the hypothesis that high-dose AAS treatment enhances endogenous opioid activity in rhesus monkeys in a way that produces opioid tolerance or dependence.     

The feasibility of quantitative analysis of androgen metabolism by use of single dermal papillae from human hair follicles

Androgenetic alopecia (AGA) is a dihydrotestosterone-mediated process, characterized by continuous miniaturization of androgen sensitive hair follicles (HF). Although increased 5 alpha-reductase (5aR) activity in affected HF is a key feature in the pathogenesis of AGA, only little is known about the in vivo expression of 5aR within AGA-affected HF. Recent studies have shown that the dermal papilla (DP) is the predominant site of type 2 5aR expression within the human HF, but direct measurements of 5aR activity in intact DP of AGA-affected HF have not been reported so far, mainly because of technical problems. Hence there is a need for a reliable and sensitive method of measuring 5aR activity in fresh tissues. As a novel approach, we used freshly isolated, intact DP and a highly sensitive HPLC-radiomatic flow scintillation system to measure 5aR. In this way we were able to measure 5aR even in small DPs from miniaturized HF. Our results show that DP from the occipital scalp express ex vivo considerable amounts of 5aR activity, but the measurable enzyme activities of individual DP differ considerably. Therefore the use of only one or two DP is at present not a reliable tool to analyze 5aR activity ex vivo.     

Thomas Bateman MD FLS 1778-1821

Thomas Bateman was a physician to the Carey Street Public Dispensary with Robert Willan in the first decade of the nineteenth century when the latter was developing the classification that would act as a foundation for modern dermatology. Following Willan's death with his work still incomplete, Bateman published a book, as an abstract of Willan's full concept, which was probably the most influential dermatology text of the nineteenth century. This was the first classification of dermatology that precisely defined the terms used and fitted individual diseases into a single class, rather than considering different stages of the same disease as maladies that belonged in different classes. This was the first attempt to link treatment to the disease process rather than to the clinical appearances and thus represents the origin of modern scientific clinical dermatology.     

Partial restoration of hair growth in the DEBR model for Alopecia areata after in vivo depletion of CD4+ T cells

Alopecia areata (AA) is widely believed to be an autoimmune disease. Hair loss is associated with a peri- and intrafollicular inflammatory infiltrate of anagen hair follicles primarily composed of CD4 + and CD8 + cells. A previous investigation involved in vivo depletion of CD8 + cells in the DEBR rat model to examine the cells' potential pathogenic activity in AA. The rat model is used here in a comparable study of CD4 + cell pathogenic activity. Eight AA affected DEBR rats were given intraperitoneal injections of a CD4 + cell depleting OX-35/OX-38 monoclonal antibody (MoAb) cocktail over a 15-day therapy course. A further eight AA-affected rats comprised a control group and were injected with equivalent volumes of an irrelevant MoAb, OX-21. Changes in both CD4 + and CD8 + peripheral blood cell populations were analysed by flow cytometry, and macrophotography was used to record any changes in hair growth. Of the eight CD4 + cell-depleted rats six responded with hair growth. The rats revealed significant hair growth within 23 days of treatment initiation. With rapid replacement of the CD4 + cell population the newly generated pelage hair was eventually lost. Two control rats also showed limited hair growth within the 112-day study period. In vivo depletion of CD4 + cells partially restores hair growth in AA affected rats. The response suggests that CD4 + cells may be actively involved in the pathogenesis of AA. Further research may elucidate whether CD4 + cells have a direct effect on hair follicles or exert their influence through their classic T helper cell supporting role for CD8 + cells.     

液氮浅低温冷冻治疗斑秃的临床观察

我们采用液氮浅低温疗法治疗斑秃72例,有效率为100％,治愈率91.7％,优于其它疗法。其作用机制,我们认为,一为直接改善了局部的血液循环,二是通过神经反射,作用于植物神经系统,使皮肤的血管舒缩障碍改善,毛囊的血液供应增加,毛发得以生长,三是通过冷冻免疫的作用。另外,浅低温冷冻疗法可能有使黑色素细胞数目和黑色素的合成增加的作用,因而新生毛发呈黑色。