WITHDRAWN: Mutational analysis of the F8 gene and phenotypic characterization of Hemophilia A.

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Correlation between cotinine urinary levels & cardiovascular autonomic function tests among smokeless tobacco chewers: A cross-sectional study.

BACKGROUND & OBJECTIVES: Cardiovascular disease (CVD), the leading cause of death worldwide is responsible for over 17 million deaths globally, of which 10 per cent deaths have been expected due to consumption of tobacco. The association between CVD and chewing of tobacco is limited and remains arguable. The aim of this study was to find out the correlation between urinary cotinine level and cardiovascular autonomic function tests of tobacco chewers. METHODS: In the present study, 600 participants, 300 smokeless tobacco chewers (STC) and 300 non-tobacco chewers (NTC), between 18 and 65 yr were selected. Various parameters such as anthropometric, systolic blood pressure (SBP), diastolic blood pressure (DBP), autonomic function tests and urinary cotinine levels were measured. RESULTS: Significant difference (P<0.001) was noted in STC and NTC for anthropometric parameters, SBP, DBP and urinary cotinine levels. Sympathetic and parasympathetic autonomic function test showed significant difference on comparison in STC and NTC groups, except in Valsalva ratio. Correlations with urinary cotinine levels were significant for sympathetic autonomic functions, SBP fall (r=0.138, P=0.016), DBP rise (r=-0.141, P≤0.014); parasympathetic autonomic function, heart rate (HR) response to standing (r=-0.208, P≤0.003), deep breathing (r=-0.473, P≤0.001) and Valsalva ratio (r=-0.396, P≤0.0001). INTERPRETATION & CONCLUSIONS: Correlation between urinary cotinine levels and autonomic function tests elucidates the linkage involving autonomic nervous system damage which can be considered as an important associated relationship for early diagnosis of CVD health risk factors among smokeless tobacco (ST) users.

Antioxidative and radioprotective potential of rutin and quercetin in Swiss albino mice exposed to gamma radiation.

The radioprotective potential of bioflavonoid, rutin (RUT) and quercetin (QRT) was investigated in Swiss albino mice exposed to gamma radiation. The radioprotective potential of RUT and QRT was assessed in pre-treatment group of mice followed on radiation-induced changes in glutathione (GSH), glutathione-S-transferase (GST), superoxide dismutase (SOD), catalase (CAT), and lipid peroxidation (LPO) levels were also analyzed. Elevation in the GSH, GST, SOD, CAT, and decreased LPO levels were observed in RUT and QRT pretreated group when compared to the irradiated animals. Furthermore, it was observed that RUT and QRT treatment was found to inhibit various free radicals generated in vitro, viz., 2,2-diphenyl-1-picrylhydrazyl(DPPH), O2, 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) (ABTS)(+), and OH in a concentration-dependent manner. This study clearly demonstrates the free radical scavenging action of RUT and QRT, indicating that it may have its potential as a radioprotective agent. Furthermore, the presence of a phenolic group in RUT and QRT is known to contribute to scavenging the radiation-induced free radicals and inhibition of oxidative stress. Present findings demonstrate the potential of RUT and QRT in mitigating radiation-induced oxidative stress, which may be attributed to the inhibition of radiation-induced decline in the endogenous antioxidant levels and scavenging of radiation-induced free radicals.

A clinical update on massive ovarian oedema - a pseudotumour?

OBJECTIVE: Benign massive ovarian oedema is a rare clinical entity arising from the ovaries, and it poses a significant clinical challenge as it can be easily mistaken for neoplasm. Due to the lack of pathognomonic clinical features or characteristic hallmarks on non-invasive diagnostic modalities and the dependence on the final histopathology, the efforts of the surgeon have been deviated from performing fertility-sparing surgery on young women. The lack of standardised guidelines due to the rarity of this condition calls for a review of the literature to enable the clinician to formulate treatment guidelines. METHODS AND MATERIAL: A Medline search on the PubMed database for literature published in English from 1969 to 2011 was done using the keywords 'massive ovarian oedema, massive ovarian oedema case report or case series, and pseudotumour of ovary'. A total of 177 women who had undergone a variety of treatments were retrieved. We also report the management options we used for four women presenting to us between August 2000 and October 2011, as well as a review of the literature. RESULT: A total of 177 cases of massive ovarian oedema were identified. Out of these cases 151 (85.3%) were primary massive ovarian oedema; secondary massive ovarian oedema was identified in 26 (14.7%) cases. A salpingo-oophorectomy was done in 145 (81.9%) cases, 12 (6.8%) cases had an abdominal hysterectomy with bilateral salpingo-oophorectomy. A total of 76 (42.9%) cases intraoperatively were found to have ovarian torsions, and one patient with primary massive ovarian oedema had ascites. Conservative treatment was carried out in 20 (11.3%) patients; 14 of these had a wedge biopsy with frozen section and with or without ovarian suspension, one patient had diagnostic laparotomy, and five cases had only ultrasonographic or magnetic resonance imaging monitoring and symptomatic treatment. The four cases treated at the regional cancer institute from 2000 to 2011 revealed that the first three cases had salpingo-oophorectomy and the fourth case received a successful conservative treatment. CONCLUSION: The majority of massive ovarian oedemas will respond to judicious use of intraoperative wedge resection and frozen section for the confirmation of diagnosis. The detorsion and transfixation of the ovary or partial debulking and drainage of fluid accumulated in the cyst may be more appropriate to preserve hormonal function and fertility in these young women.

Kindling & mossy fibre sprouting in the rat hippocampus following hot water induced hyperthermic seizures.

BACKGROUND & OBJECTIVES: Hot water epilepsy (HWE) is well recognized reflex epilepsy with possible genetic susceptibility. Rat model and human experimentation had proven that HWE is a type of hyperthermic seizure with possible kindling on repeated stimulation in animals. The present study was undertaken to investigate kindling associated with hyperthermic seizures induced by repeated hot water stimulation in the rat model and to prove hyperthermic kindling. METHODS: Epileptic seizures were induced in 36 male Wistar albino rats by means of hot water sprays at 48 h time intervals. Progression of seizure activity was investigated by studying the behaviour, severity and duration of the seizure. Threshold of rectal temperatures and timed latency for seizure induction were studied. Seizure discharges (EEG) were recorded from ventral hippocampus in six of these rats. Timm's staining was used to study the neuronal sprouting as a consequence of kindling. Studying the seizure threshold, latency, duration of seizure discharge and behavioural seizure following a stimulus-free interval of 30 days tested permanence of kindling. RESULTS: Following 8-12 episodes of hot water stimulations there was progressive epileptic activity manifested in the form of lowering of rectal temperature thresholds from 41.5 to 40.0 degrees C, drop in latency for developing seizures from 185 to 118 sec, increase in duration of hippocampal seizure discharge from 15 to 140 sec, along with progressive increase in complexity of EEG after discharges, increase in behavioural seizure severity from Grade 1 to 5 in all the rats, and neuronal sprouting observed in supragranular molecular layer and in stratum lacunosum. INTERPRETATION & CONCLUSION: Our study covered all aspects of kindling and provided a useful animal model for human hot water epilepsy. Hyperthermic seizures induced by hot water in the rat model kindle as demonstrated by Timm's staining.

Chemical genetics identifies Rab geranylgeranyl transferase as an apoptotic target of farnesyl transferase inhibitors.

A chemical genetics approach identified a cellular target of several proapoptotic farnesyl transferase inhibitors (FTIs). Treatment with these FTIs caused p53-independent apoptosis in Caenorhabditis elegans, which was mimicked by knockdown of endosomal trafficking proteins, including Rab5, Rab7, the HOPS complex, and notably the enzyme Rab geranylgeranyl transferase (RabGGT). These FTIs were found to inhibit mammalian RabGGT with potencies that correlated with their proapoptotic activity. Knockdown of RabGGT induced apoptosis in mammalian cancer cell lines, and both RabGGT subunits were overexpressed in several tumor tissues. These findings validate RabGGT, and by extension endosomal function, as a therapeutically relevant target for modulation of apoptosis, and enhance our understanding of the mechanism of action of FTIs.

Maxillary palp glomeruli and ipsilateral projections in the antennal lobe of Drosophila melanogaster.

The antennal lobe was examined by Golgi-silver impregnation to differentiate the glomeruli depending on the source and types of inputs. Thirty-five of the 43 'identified' olfactory glomeruli were Golgi-silver impregnated in the present study. Seven glomeruli compared to three, reported previously, were found to be targets of maxillary palp chemosensory neurons. These include glomeruli VA3, VC2, VM5, VA7m/VA7l of the ventral antennal lobe and DC2, DC3, DM5 of the dorsal antennal lobe. The number of glomeruli receiving the maxillary palp sensory projections tallies with the number of Drosophila olfactory receptors (seven) reported to be expressed exclusively in the maxillary palp. Twenty-eight Golgi-impregnated glomeruli were found to receive input from the antennal nerve. The ratio of glomeruli serving the maxillary palp to those serving the antenna (approximately 1:5) matches with the ratio of Drosophila olfactory receptors expressed in these two olfactory organs respectively. In addition to glomerulus V, glomeruli VP1-3, VL1, VL2a/2p and VC3m/3l were found to receive ipsilateral projections. Thus, additional ipsilateral glomeruli have been identified.