Synthesis, anti-inflammatory evaluation and docking studies of some new fluorinated fused quinazolines.

A series of novel 8/10-trifluoromethyl-substituted-imidazo[1,2-c] quinazolines have been synthesized and evaluated in vivo (rat paw edema) for their anti-inflammatory activity and in silico (docking studies) to recognize the hypothetical binding motif of the title compounds with the cyclooxygenase isoenzymes (COX-1 and COX-2) employing GOLD (CCDC, 4.0.1 version) software. The compounds, 9b and 10b, were found to have good anti-inflammatory activity [around 80% of the standard: indomethacin]. The binding mode of the title compounds has been proposed based on the docking studies.

Cloning of gonadotropin-releasing hormone I complementary DNAs in songbirds facilitates dissection of mechanisms mediating seasonal changes in reproduction.

Temperate zone animals exhibit seasonal variation in reproductive physiology. In most cases, seasonal changes in reproductive states are regulated by changes in GnRH1 secretion, rather than synthesis, from the preoptic area (POA)/anterior hypothalamus. An important exception occurs in some songbirds that become photorefractory to the stimulatory effects of long days and show profound decreases in brain GnRH1 protein content. Whether this decline reflects changes in gene expression is unknown because of past failures to measure GNRH1 mRNA levels, due in large part to the absence of available GNRH1 gene sequence in this taxon. Here, we report the first cloning of GNRH1 cDNAs in two songbirds: European starlings and zebra finches. Consistent with the size of the prepro-hormone in other avian and non-avian species, the open-reading frames predict proteins of 91 and 92 amino acids, respectively. Whereas the decapeptide in both species is perfectly conserved with chicken GnRH1, the amino acid identity in the signal peptide and GNRH associated peptide subdomains are significantly less well conserved. At the nucleotide level, the starling and zebra finch coding sequences are approximately 88% identical to each other but only approximately 70% identical to chicken GNRH1. In situ hybridization using radiolabeled cRNA probes demonstrated GNRH1 mRNA expression primarily in the POA, consistent with previous studies on the distribution of the GnRH1-immunoreactive cell bodies. Furthermore, we provide evidence for photoperiod-dependent regulation of GNRH1 mRNA in male starlings. Declines in GNRH1 mRNA levels occur in parallel with testicular involution. Thus, photorefractoriness is associated with decreases in GNRH1 gene expression in the medial POA.

Footwear and foot care knowledge as risk factors for foot problems in Indian diabetics.

We assessed 300 diabetic and 100 age- and sex-matched controls for correlating foot wear practices and foot care knowledge and the presence of foot complications. A structured questionnaire evaluated the knowledge about foot care, type of footwear used, education level, association of tobacco abuse, and any associated symptoms of foot disease. Clinical evaluation was done by inspection of feet for presence of any external deformities, assessment of sensory function (vibration perception threshold, VPT), vascular status (foot pulses and ankle brachial ratio) and presence of any infection.In the diabetes category, 44.7% patients had not received previous foot care education. 0.6% walked barefoot outdoors and 45% walked barefoot indoors. Fourteen (4.7%) patients gave history of foot ulceration in the past and comprised the high risk group; only 2 out of 14 had received foot care education, 6 gave history of tobacco abuse, 8 had symptoms of claudication, 9 had paresthesias, 2 walked barefoot indoors. Average duration of diabetes in the high-risk and low-risk diabetes group was 10.85 +/- 6.53 and 9.83 +/- 7.99 years, respectively. In the high- and low-risk diabetic groups, VPT was 19.57 +/- 11.26 and 15.20 +/- 10.21V (P < 0.02), ankle brachial ratio was 1.05 +/- 0.19 and 1.14 +/- 0.18 (P < 0.05), and the questionnaire scores was 40.8% and 57%, respectively.In the diabetic and the control group, VPT was 15.62 +/- 10.39 and 8.36 +/- 3.61 V (P < 0.01), ankle brachial ratio was 1.14 +/- 0.18 and 1.15 +/- 0.12, and the questionnaire scores were 57% and 40.3%, respectively.In conclusion, poor knowledge of foot care and poor footwear practices were important risk factors for foot problems in diabetes.

Effect of (Ala8,13,18)-magainin II amide on human trophoblast cells in vitro.

Magainins are cationic peptides with anti-bacterial and anti-tumor properties. The anti-nidatory function of a synthetic analogue of magainin, (Ala8,13,18)-magainin II amide, has earlier been reported, and it has been indicated that placental trophoblast cells could be a target of magainin resulting in its contragestational action. The aim of the present study was to examine the effect of (Ala8,13,18)-magainin II amide (100 ng/ml and 1000 ng/ml) on attachment efficiency, viability, differentiation in terms of hCG secretion and invasive function of isolated first trimester, human placental trophoblast cells grown on rat-tail collagen type-I matrix in primary cell culture. In the present experimental model, magainin was not found to affect human trophoblast cell functions in vitro.

Evaluation of a short course on diabetology for practising doctors.

A short course on Diabetology, attended by 83 doctors was evaluated. The doctors were divided into three groups. (Group I--basic qualification MBBS, Group II--MD in medicine or allied subject, Group III--Diploma in Diabetes Mellitus). The mean age group of all three groups were comparable. Pre-course evaluation of their knowledge of diabetes showed the best performance in Group III and poorest in Group I. Post-course evaluation showed significant improvement only in Group I and II. Maximal improvement in performance was seen in Group II. Mean time since passing the last professional examination was 14.8, 12.6 and 1.0 year respectively. The performance was not linked to time since passing the last examination. 14.5% of doctors were from a rural or semiurban setting. The precourse performance of rural doctors in the MD group was significantly poorer, but their post course performance was as good as the others. All doctors from rural or semiurban areas improved their performance postcourse, compared to 84% in the urban group. 74% of doctors had not attended any post graduate course after their basic degree. Their performance did not differ significantly from those who had attended such courses. 44.6% were Consultants, 26.6% were general practitioners, 12.0% were attached to institutions, 10.8% were in government service or armed forces and 6% were attached to teaching hospitals. The performance of the doctors was not linked to the type of practice. The doctors attending the course felt that the audiovisual presentation needed improvement.

Short-term results of initial trabeculectomy with intraoperative or postoperative 5-fluorouracil for primary glaucomas.

Thirty-three eyes of 33 patients were prospectively evaluated to study the short term efficacy, safety, and overall surgical outcome of initial trabeculectomy for primary glaucomas with adjunctive intraoperative or postoperative 5-Fluorouracil (5-FU) use. Twelve eyes serving as controls underwent trabeculectomy without adjunctive antimetabolites. Eleven eyes received intraoperative 5-FU, while 10 eyes received subconjunctival 5-FU postoperatively. Intraocular pressure (IOP) was maintained below 22 mmHg at 3 months of follow up in 90.9% and 80% of patients in the intraoperative and postoperative 5-FU groups, respectively, without use of additional antiglaucoma medications, whereas 66.7% of the patients in the control group achieved similar IOP levels. Hypotony (IOP < 6 mmHg) was seen more commonly after intraoperative 5-FU (27.3%). Corneal epithelial defects were seen exclusively in the postoperative 5-FU group (40%). The use of intraoperative 5-FU exclusively as a mode of antimetabolites delivery seems an acceptable alternative to enhance success rates of trabeculectomy for the primary glaucomas.

Short-term results of initial trabeculectomy with intraoperative or postoperative 5-fluorouracil for primary glaucomas.

Thirty three eyes of 33 patients were prospectively evaluated to study the short term efficacy, and overall surgical outcome of initial trabeculectomy for primary glaucomas with adjunctive intraoperative on postoperative 5-Fluorouracil (5-FU) use. Twelve eyes served as control who underwent trabeculectomy without adjunctive antimetabolites. Eleven eyes received intraoperative 5-FU, while 10 eyes received subconjunctival 5-FU postoperatively. Intraocular pressure (IOP) was maintained below 22 mmHg at 3 months of follow up in 90.9% and 80% of patients in the intraoperative and postoperative 5-FU groups respectively, without use of additional antiglaucoma medications, whereas 66.7% of the patients in the control group achieved similar IOP levels. Hypotony (I.O.P. < 6 mmHg) was seen more commonly after intraoperative 5-FU (27.3%). Corneal epithelial defects were seen exclusively in the postoperative 5-FU group (40%). The use of intraoperative 5-FU exclusively as a mode of antimetabolite delivery seems an acceptable alternative to enhance success rates of trabeculectomy for the primary glaucomas.

Spontaneous extrusion of extraocular cysticercus cysts.

PURPOSE: We treated two patients who had spontaneous extrusion of cysticercus cysts and subconjunctival swelling. Additionally, one patient had severe myositis and restriction of ocular movements. METHODS: The patients were prescribed oral albendazole, 15 mg/kg of body mass per day. Systemic corticosteroids were also given to the patient who had severe myositis. RESULTS: Spontaneous extrusion of the cysts occurred in both patients within three to five days of starting albendazole therapy. The conjunctival defects healed without any surgical intervention. The ocular motility in the patient with myositis returned to normal. CONCLUSION: As extrusion happened soon after the start of albendazole therapy, it is uncertain whether this therapy played any role. Additionally, it is not clear if systemic therapy must be continued in the absence of systemic and neurologic manifestations.

GAS POISONING WITH FREON-12 (A Report of Three Cases).

Three pauents of accidental gas poisoning with Freon-12 are reported. Presenting features were transient loss of consciousness, bradycardia, hypotension and anaesthesia. All patients made a rapid and uneventful recovery without any residual effects.

Serum sialic acid levels in patients with sympathetic ophthalmitis.

Serum sialic acid levels were measured in 16 patients with sympathetic ophthalmitis, 36 with neglected traumatic uveitis following penetrating injury and 40 healthy subjects. There was no significant alteration of its level in patients with traumatic uveitis. However, its level was significantly elevated in patients with sympathetic ophthalmitis. It was high even in the early stage of the disease. It decreased significantly at the remission stage. It is proposed that measurement of sialic acid level in serum can be used as a diagnostic aid when the diagnosis of sympathetic ophthalmitis remains doubtful on clinical grounds. The extent of rise in its level may be considered a good parameter of the degree of severity of sympathetic ophthalmitis. It may also act as a useful tool to evaluate the drug efficacy in this disease.

Multiple neoplasia in a patient with pituitary acromegaly.

A case of pituitary acromegaly with multiple nonendocrine neoplasia is reported. The tumorogenic potential of growth hormone, prolactin and other growth factors is discussed.

Leprotic keratopathy in India.

Corneal affections cause severe ocular morbidity in leprosy. Poor nutrition and low socio-economic status make the eyes prone to repeated secondary infections which makes the pattern of corneal disease in this country different from that reported in western literature. A study of 250 patients shows that leprotic keratopathy has 4 different patterns. Primary leprous keratitis was seen in 56.5% of cases, while secondary leprous keratitis (groups B, C & D) constituted 57.7%. In the latter group the ocular morbidity could be prevented by controlling infection and prevention of concomitant diseases. Cases of lepromatous leprosy showed a consistently higher incidence of different types of corneal involvement than tuberculoid cases.

Factors influencing corneal involvement in leprosy.

Corneal involvement in leprosy is known to be influenced by factors such as lagophthalmos, ectropion, and corneal anesthesia. In the present study conducted on 400 eyes of leprosy patients, observations were made on tear film abnormalities, and their relation to the above-mentioned factors was analyzed. The abnormality of tear film breakup time (BKUT) was found to be clinically more significant (47.2%) than a Schirmer's test alone (24.5%), and this finding was of greater significance in the lepromatous form of leprosy. An abnormal BKUT reflects a decreased mucin secretion by the conjunctival goblet cells. Tear film abnormalities in association with lagophthalmos, corneal anesthesia, concomitant ocular diseases, and environmental factors such as high relative humidity have been identified as factors contributing to corneal involvement in leprosy in India. It is not surprising that with so many mechanisms of corneal involvement the clinical manifestations are diverse, and all forms of pathological changes may contribute to corneal morbidity.