Modeling non-syndromic autism and the impact of TRPC6 disruption in human neurons.

An increasing number of genetic variants have been implicated in autism spectrum disorders (ASDs), and the functional study of such variants will be critical for the elucidation of autism pathophysiology. Here, we report a de novo balanced translocation disruption of TRPC6, a cation channel, in a non-syndromic autistic individual. Using multiple models, such as dental pulp cells, induced pluripotent stem cell (iPSC)-derived neuronal cells and mouse models, we demonstrate that TRPC6 reduction or haploinsufficiency leads to altered neuronal development, morphology and function. The observed neuronal phenotypes could then be rescued by TRPC6 complementation and by treatment with insulin-like growth factor-1 or hyperforin, a TRPC6-specific agonist, suggesting that ASD individuals with alterations in this pathway may benefit from these drugs. We also demonstrate that methyl CpG binding protein-2 (MeCP2) levels affect TRPC6 expression. Mutations in MeCP2 cause Rett syndrome, revealing common pathways among ASDs. Genetic sequencing of TRPC6 in 1041 ASD individuals and 2872 controls revealed significantly more nonsynonymous mutations in the ASD population, and identified loss-of-function mutations with incomplete penetrance in two patients. Taken together, these findings suggest that TRPC6 is a novel predisposing gene for ASD that may act in a multiple-hit model. This is the first study to use iPSC-derived human neurons to model non-syndromic ASD and illustrate the potential of modeling genetically complex sporadic diseases using such cells.

Laparoscopic management of transverse testicular ectopia with persistent mullerian duct syndrome.

A 4-month-old male child presented with right undescended testis and left inguinal hernia with funiculitis. Ultrasonography showed funiculitis on the left side testis along with presence of 1.5 × 1 cm testis like structure just above left testis and empty right scrotal sac without any evidence of mullerian structures. On diagnostic laparoscopy, right testicular vessels were crossing from right to left and had uterus with both testes in left hernia sac. Mobilization of vessels, division of uterus, and hernia repair was done laparoscopically. On the review of literature, there is only one case report of total laparoscopic repair of transversetesticular ectopia (TTE) with hernia without persistent mullerian duct (PMDS). The uniqueness of our case is that it had TTE with hernia and PMDS, which were totally managed by laparoscopy. On 6 months of follow-up, both the testes are palpable in scrotum.

A review on plant-derived natural products and their analogs with anti-tumor activity.

Traditional medicines, including Chinese herbal formulations, can serve as the source of potential new drugs, and initial research focuses on the isolation of bioactive lead compound(s). The development of novel plant-derived natural products and their analogs for anticancer activity details efforts to synthesize new derivatives based on bioactivity- and mechanism of action-directed isolation and characterization coupled with rational drug design - based modification. Also, the anticancer activity of certain natural products and their analogs can be enhanced by synthesizing new derivatives based on active pharmacophore models; drug resistance and solubility and metabolic limitations can be overcome by appropriate molecular modifications; and new biological properties or mechanisms of action can be added by combining other functional groups or molecules. Preclinical screening for in vitro human cell line panels and selected in vivo xenograft testing then identifies the most promising drug development targets.

Haematology and serum biochemistry of chital (Axis axis) and barking deer (Muntiacus muntjak) reared in semi-captivity.

Haematological and serum biochemical values of clinical significance that could serve as reference data for deer kept in captivity were measured for chital (Axis axis) and barking deer (Muntiacus muntjak). The venous blood from four each of chital and barking deer (n = 8) reared in semi-captivity was collected after proper restraint of the animals. The mean blood haemoglobin, packed cell volume, total erythrocyte count and total leukocyte count of all the eight deer of the two species were 15.90 +/- 0.44 g/dl, 51.44 +/- 0.60%, 20.83 +/- 0.57 x 10(6)/microl and 2.37 +/- 0.20 x 10(3)/microl. Serum total protein, albumin, bilirubin, cholesterol and blood urea nitrogen irrespective of species were 6.83 +/- 0.19 g/dl, 3.90 +/- 0.11 g/dl, 0.33 +/- 0.08 mg/dl, 106.81 +/- 3.59 mg/dl and 24.79 +/- 2.11 mg/dl, respectively. Serum enzyme activities indicative of liver function such as alanine transaminase (ALT) and aspartate transaminase (AST) were 30.38 +/- 4.67 units/ml and 42.88 +/- 5.97 units/ml, respectively. The serum calcium and phosphorus levels of all the eight deer were 10.27 +/- 0.36 mg/dl and 8.31 +/- 0.68 mg/dl, respectively. This is the first report on baseline values in barking deer. The distribution of haematological and serum biochemical values was fairly normal, suggesting that the mean values could be representative of normal values for two different deer species.

Successful therapeutic management of canine Isosporosis in puppies.

Four labrador male puppies were confirmed for the Isospora spp infection by direct smear and flotation method following complains of anorexia, haematemesis and haematochezia. The puppies were treated with trimethoprime and sulphamethoxazole @ 40 mg/kg body weight in combination with metronidazole @ 10 mg/kg body weight twice daily for 5 days which was supported with fluid therapy, aniemetics and plasma expanders. All the animals showed completed clinical recovery along with clearing of faecal oocyst.

Effect of Tamarindus indica leaf powder on plasma concentrations of copper, zinc, and iron in fluorotic cows.

AIM: The main objective of the study was to determine the deleterious effect of fluoride on plasma trace minerals of fluorotic cattle and to evaluate the effect of Tamarindus indica leaf powder toward correction of the same. MATERIALS AND METHODS: A total of 30 cattle exhibiting chronic sign of fluorosis and 10 healthy cattle from nonfluorotic area were incorporated in this study. Fluorotic cattle were divided into three equal groups consisting of 10 cattle each. Group I from fluoride free area served as healthy control. The Group II received no treatment and served as disease control. Groups III and IV were supplemented with tamarind leaf powder at 15 g and 30 g/day with feed for 60 days. Plasma mineral status was evaluated after 60 days of treatment with double beam atomic absorption spectrophotometer. RESULTS: Statistical analysis of data revealed a significant (p<0.05) decrease in mean plasma copper (Cu) (0.344±0.007 ppm), zinc (Zn) (0.692±0.06 ppm), and iron (Fe) concentration (1.100±0.01 ppm) in fluorotic cattle in comparison to healthy cattle (0.58±0.010, 2.342±0.04, 1.406±0.04 ppm, respectively). Significant (p<0.05) increase in Cu, Zn, and Fe was recorded after supplementation of tamarind leaf powder to the fluorotic cattle. CONCLUSION: It was concluded that fluorotic cattle might be supplemented with T. indica leaf powder with feed for the correction of the decreased level of certain plasma minerals.

Concurrent infestation of Notoedres, Sarcoptic and Psoroptic acariosis in rabbit and its management.

Acariotic mange in rabbits is one of the important constraints in rabbit husbandry. Sarcoptes scabies var. cuniculi and Psoroptes cuniculi are most common mites prevailed in rabbits, but Notoedres cati, is the rarest mite ever been reported in rabbit. Two New Zealand white rabbits were presented with clinical signs of pruritus, alopecia, scab and crust formation and lichenification on the upper lip, ear pinnae, eyelids, lower jaw and limbs. Deep skin scraping was taken separately from 4 to 5 different skin lesions from each rabbit, revealed mixed infestations of N. cati, S. cuniculi and P. cuniculi. Subcutaneous injection of ivermectin at weekly intervals for four weeks resulted in remission of clinical signs and improvement of health condition in rabbits. This is the first report of N. cati infestation of rabbit in Odisha.

Comparative anthelmintic efficacy of ivermectin delivered through different routes in gastrointestinal nematode infected dogs.

Ivermectin is one of the most effective and widely used antiparasitic agents ever discovered because of its broad spectrum activity against nematodes and arthropods. Therefore, the study was conducted to determine the comparative anthelmintic efficacy of ivermectin by giving through oral and subcutaneous routes in clinically infected dogs and also to check the prevalence of gastrointestinal nematode in dogs in Bhubaneswar, Odisha. Total 154 dogs with clinical signs of gastroenteritis were examined for the presence of nematodal ova in their faecal sample and 64 were found positive (41.56 %). The screened dogs were divided in to two groups (n = 10 each), first group of animals were treated with ivermectin @ 0.5 mg/kg body weight by subcutaneous route and the second group with same dose of ivermectin through oral route. Efficacy of ivermectin was evaluated based on egg per gram (EPG), haematological and biochemical parameters. It is concluded that, Prevalence of gastrointestinal nematodes are high in dogs in the climatic condition of Bhubaneswar, Odisha. Ivermectin was found effective when administered through either of the routes. Haemato-biochemical parameters were restored after administration of ivermectin and also significant reduction in EPG was found in dogs treated with ivermectin by both the routes, but no significant difference was observed in EPG between oral and subcutaneous treated dogs in various intervals of study.

Basic fibroblast growth factor induces a transformed phenotype in normal human melanocytes.

Basic fibroblast growth factor (bFGF or FGF-2) is produced by nearly all melanomas in vitro and in vivo but not by normal melanocytes, which require exogenous bFGF for growth. In this study, we transduced normal human melanocytes to overexpress two forms of bFGF: (bFGF-Long and bFGF-Short) using replication-deficient adenovirus 5 vectors. bFGF-Long induced the 17.8, 22.5, 23.1 and 24.2 kDa forms of bFGF, whereas bFGF-Short induced only the 17.8 kDa mature form. Growth of cultured melanocytes transduced with either vector was similar to that of nevus and melanoma cells and was independent of exogenous bFGF and of insulin/insulin-like growth factor 1, and cyclic AMP enhancers, requiring only phorbol ester as an exogenous mitogen. Like primary melanoma cells, transduced normal melanocytes grew anchorage independently in soft agar. When injected into the dermis of human skin grafted to mice, bFGF-transduced melanocytes proliferated for at least 20 days, whereas cells from control cultures showed poor survival and no proliferation. These results demonstrate that bFGF upregulation is a critical component in melanoma progression.

Effect of Moringa oleifera on hematological parameters of calves reared in industrial fluorotic area.

AIM: The present study was undertaken to evaluate the ameliorative potential of dried Moringa oleifera fruit powder in fluorosis affected calves reared around the vicinity of aluminium smelter plant. MATERIALS AND METHODS: Total 107 calves were screened on the basis of clinical signs and higher plasma fluoride (more than 0.2 ppm) level for evidence of fluorosis. Out of that, 90 samples found positive and from them 18 calves of 6-12 months age group were selected and divided equally into three groups named as Group II, III, and IV. Group II remained as disease control group whereas Group III calves were supplemented with dried M. oleifera fruit powder of 25 g/calve for 60 days. Group IV calves were supplemented with calcium carbonate at 100 mg/kg body weight and boric acid at 10 mg/kg for the same experimental period. Group I consisted of six numbers of healthy calves taken from the non-fluorotic zone, i.e. Bhubaneswar. Plasma fluoride level, hemoglobin (Hb), packed cell volume (PCV), total leukocyte count (TLC), differential count (DC), total erythrocyte count, mean corpuscular volume (MCV), mean corpuscular Hb (MCH), and MCH concentration (MCHC) were estimated on day 0, 30, and 60 of the experiment. RESULTS: Supplementation of dried M. oleifera fruit powder to fluorosis affected calves resulted in significant reduction in plasma fluoride level and increase in Hb%, PCV, TLC and altered DC. Similar results were also recorded in calcium+boron group, except PCV and Hb. No significant changes were observed in MCV, MCH, and MCHC values. CONCLUSION: The present study concluded that supplementation of dried M. oleifera fruit powder daily for 60 days has shown protection against chronic fluoride toxicity in calves.

Magnesium protects against cocaine-induced hemorrhagic stroke in a rat model: a 31P-NMR in-vivo study.

In-vivo 31P-nuclear magnetic resonance (NMR) studies were undertaken with anesthetized rats to determine: a. whether systemic administration of MgCl2 could protect animals against cocaine-induced hemorrhagic stroke, and b. whether a relationship exists between basal levels of brain intracellular free magnesium ions ([Mg2+]i), phosphometabolites, and stroke risk. Repeat 31P-NMR spectra were obtained at various intervals of time (3-120 min, or up until death) after administration of cocaine (5 + 30 mg/kg). Ion selective electrodes were used to measure plasma Mg2+, K+, Na+ and Ca2+. Forty percent of animals died in the absence of Mg2+ infusion following high dosage of cocaine. Only 13% died with cocaine following Mg2+ infusion (p <0.005). In the Mg2+-protected animals, neither brain [Mg2+]i,intracellular pH (pHi), [phosphocreatine-PCr]/[ATP], nor brain [inorganic phosphate-Pi]/[ATP] fell when toxic and lethal doses of cocaine were given. Low basal brain [Mg2+]i (275 +/- 24 vs. 466 +/- 35 microM, p <0.01) and low basal brain [PCr] (3.36 +/- 0.35 vs. 4.26 +/- 0.24 mM, p <0.01) were found to be associated with a 3-fold increased incidence of stroke. A positive correlation (r = 0.31, p <0.03) between brain [Mg2+]1 and [PCr]/[ATP] was found. It is possible that both brain [Mg2+]i and [PCr] may be useful as important predictors of susceptibility to cocaine-induced hemorrhagic stroke.

The International Health Program: the fifteen-year experience with Yale University's Internal Medicine Residency Program.

The purpose of this study was to assess the impact of international health electives on physicians-in-training. A retrospective study was conducted using an anonymous, self-administered mailed survey to internal medicine residents who trained at Yale from 1982 to 1996 based on their experience with our International Health Program (IHP). The response rate was 61%, with 96 completed surveys in the participant group and 96 completed surveys in the nonparticipant group. Participants were more likely than nonparticipants to care for patients on public assistance (77 versus 49; P < 0.001) and immigrant patients (41 versus 23; P = 0.006). Among residents who changed their career plans, participants (22) were more likely than nonparticipants (14) to switch from subspecialty medicine to general medicine (P = 0.02). Participants were significantly more likely to have a positive view of health care delivery in developing countries. Compared with nonparticipants (64), IHP participants (74) believed that the physical examination is under-used by physicians from the United States as a diagnostic skill (P = 0.03). International health experiences appeared to have an important impact on the decisions and attitudes of residents.

Generation of transgenic mice for studies of ocular development and disease.

Over the past decade, there has been spectacular growth in our understanding of the molecular genetics of eye development and ocular disease. Although this is primarily caused by developments in recombinant DNA technology, it is also caused in large part by advances in, and the spread of, transgenic mouse technology. Whereas 10 years ago few laboratories had the equipment and skill to generate transgenic mice, now most investigators have access to a transgenic core facility. Transgenic mouse studies have fueled our understanding of ocular development, have delineated regulatory elements involved in gene expression in cells of the eye, and have unraveled pathogenic mechanisms involved in eye disease.

Epidemiology of basal cell carcinoma and squamous cell carcinoma of the pinna.

This is a retrospective study designed to compare the incidence of basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) in the head and neck skin area with special reference to the pinna. The results showed 426 patients had 460 cutaneous malignancies in the head and neck area, managed by four specialties (ENT, Dermatology, General Surgery and GPs) over the period 1994-99. The lesions comprised 375 (80.47 per cent) BCC and 85 (18.47 per cent) SCC. In cases of BCC the facial areas were commonly involved (88 per cent), whilst SCC was almost equally distributed between the most (face, forehead and nose) and least exposed areas (pinna and scalp). The overall ratio of BCC to SCC remained four to one in the head and neck area. In 41 patients with 51 lesions over the pinna there were 29 (56.8 per cent) BCC and 22 (43.1 per cent) SCC hence the ratio was 1.3 to 1 for this site. We conclude that in the case of a suspicious lesion over the pinna, the risk of SCC is comparatively much higher. With increasing awareness of early and quick diagnosis of cancer cases, it is recommended that these patients should be referred urgently to prevent the significant morbidity associated with invasive SCC.

Antibiotic production by submerged culture of Melanconis flavovirens (Otth) Wehm.

The pyrenomycete Melanconis flavovirens under submerged cultivation produced antibiotics active against both bacteria and fungi. Glucose and corn-steep liquor were the best C and N sources for the antibiotic production, respectively. Supplementation with Tween-80 and enthylene glycol stimulated both antifungal and antibacterial antibiotic production, whereas oleic acid only the antifungal one. Addition of K2HPO4 also showed a positive effect. The optimal conditions for fermentation of the antifungal component are given.

An endoscopic silastic keel for anterior glottic webs.

The use of a specially designed silastic keel endoscopically inserted into the larynx to prevent restenosis after division of anterior commisure webs of the larynx is described. The treatment of such webs is discussed.

Traumatic neuroma of the internal laryngeal nerve as a cause of severe cough.

We present a case of traumatic neuroma, describing an unusual symptom which may be more common than is recognized, and indeed we think from our search of the literature that this is the first report of such a case. We have briefly reviewed the pathology, clinical presentation and treatment of traumatic neuromas.

Jugulotympanic paraganglioma (glomus jugulare tumour) presenting as a parotid neoplasm (a case report and review of the literature).

A case of glomus jugulare tumour which presented as a parotid swelling, is reported. The patient also had facial palsy, total deafness and a polypoid lesion in the auditory canal. She was treated by surgery and radiotherapy. In this paper we review the literature and discuss the diagnostic problems and significance of long-standing facial palsy.

Post-laryngectomy pharyngo-cutaneous fistulae.

A personal series of 66 total laryngectomy cases is presented with special reference to post-operative fistula formation. The incidence of fistulae was 7.4 per cent. We could not verify previous reports that any specific factors were significantly related to fistula formation and we feel that operative technique and the post-operative drainage of any fluid collection under the flaps, are the most important ways of reducing the complication of a fistula to a minimum.

Radiation induced tumours of the pharynx--can they be avoided?

Three patients who developed a post-cricoid carcinoma 5-21 years after radiotherapy for carcinoma of the larynx are presented. These patients received radiotherapy when they were young. It is suggested that alternative forms of treatment, especially partial laryngectomy with the aid of a laser should be considered in the primary management of small tumours of the larynx of young patients.