Antiphospholipid antibodies--our experience

Antiphospholipid antibodies (APA) have aroused multispeciality interests. In our study of 200 cases worked up for APA, we have used a few simple coagulation tests to detect lupus anticoagulant (LA) and ELISA to detect anticardiolipin antibodies. The positivity rate for LA among cases with recurrent pregnancy loss was 4.16% and for aCL 20.8%. The positivity rate for LA in patients with venous thrombosis was 6.2%, in arterial thrombosis was 7.14% and in SLE patients was 58.3%. In conclusion APAs are to be looked for in cases of recurrent pregnancy loss, thrombosis in people < 45 years of age without risk factors and SLE patients to assess the thrombotic risk and to decide on anti coagulant therapy for further management.     

Anti-malarial activity of some xanthones isolated from the roots of Andrographis paniculata

Four xanthones were isolated from the roots of Andrographis paniculata using a combination of column and thin-layer chromatographic methods. They were characterized as (i) 1,8-di-hydroxy-3,7-dimethoxy-xanthone, (ii) 4,8-dihydroxy-2,7-dimethoxy-xanthone, (iii) 1,2-dihydroxy-6,8-dimethoxy-xanthone and (iv) 3,7,8-trimethoxy-1-hydroxy xanthone by IR, MS and NMR spectroscopic methods. In vitro study revealed that compound 1,2-dihydroxy-6,8-dimethoxy-xanthone possessed substantial anti-plasmodial activity against Plasmodium falciparum with its IC(50) value of 4 microg ml(-1). Xanthones bearing hydroxyl group at 2 position demonstrated most potent activity while xanthones with hydroxyl group at 1,4 or 8 position possessed very low activity. In vivo anti-malarial sensitivity test of this compound on Swiss Albino mice with Plasmodium berghei infection using Peters' 4-day test gave substantial reduction (62%) in parasitaemia after treating the mice with 30 mg kg(-1) dose. In vitro cytotoxicity against mammalian cells revealed that 1,2-dihydroxy-6,8-dimethoxy-xanthone is non-cytotoxic with its IC(50) > 32 microg ml(-1).     

Widespread occurrence of the Plasmodium falciparum chloroquine resistance transporter (Pfcrt) gene haplotype SVMNT in P. falciparum malaria in India

The Plasmodium falciparum chloroquine resistance transporter (Pfcrt) K76T mutation and haplotype (amino acids 72-76) and the P. falciparum multidrug resistance 1 (Pfmdr1) mutation (N86Y) were analyzed as markers of chloroquine resistance in the DNAs of 73 blood samples from patients with P. falciparum malaria in India. Seventy of the 73 DNAs had the Pfcrt K76T mutation. Of these, 66 had the SVMNT haplotype and four had CVIET, the African/Southeast Asian haplotype. Only 20 of 69 DNAs had the Pfmdr1 N86Y mutation. It is surprising that the Pfcrt haplotype in India is predominantly SVMNT, rather than that seen in Southeast Asia. The widespread prevalence of the Pfcrt K76T mutation is a cause for concern.     

Endoscopic management of pancreatic fistula after pancreatic and other abdominal surgery

Post-operative pancreatic fistulae represent a challenge for all the actors in gastroenterology: for surgeons, because they want to prevent and treat conservatively this complication since re-operation is associated with high morbidity and mortality rates; for radiologists, because they have to provide the best staging and informations without any additional risk; and for endoscopists, because endoluminal treatment is emerging as a safe and effective procedure provided it is performed in highly experienced tertiary centres in the setting of a multidisciplinary approach. Herein, we review the definitions, the causes, the staging and the possible options to prevent or treat post-operative pancreatic fistulae. Special attention is paid to the endoscopic management of this complication: including the relief of ductal obstructions, the stenting of leakages and the drainage of bulging or non-bulging fluid collections. Practical problems and issues are clearly outlined as well as the need for future improvements in staging and management of the patients having such complications.     

TRPV1 and CB(1) receptor-mediated effects of the endovanilloid/endocannabinoid N-arachidonoyl-dopamine on primary afferent fibre and spinal cord neuronal responses in the rat

N-arachidonoyl-dopamine (NADA) is an endogenous ligand at TRPV1 and CB(1) receptors, which are expressed on primary afferent nociceptors. The aim of this study was to determine contributions of proposed pronociceptive TRPV1 and antinociceptive CB(1) receptors to effects of peripheral NADA on primary afferent fibre function. Effects of NADA on primary afferent nociceptor function, determined by whole cell patch clamp and calcium imaging studies of adult dorsal root ganglion (DRG) neurons, were determined. Application of NADA (1 microm) to DRG neurons depolarized the resting membrane potential (Vm) from -58 +/- 1 to -44 +/- 3 mV (P < 0.00001) and evoked a significant increase (P < 0.0001) in intracellular calcium (74 +/- 11% of response to 60 mm KCl), compared to basal. The TRPV1 receptor antagonist capsazepine abolished NADA-evoked depolarization of Vm (P < 0.0001) and NADA-evoked calcium responses (P < 0.001), which were also blocked by the CB(1) receptor antagonist SR141716A (P < 0.001). Effects of NADA (1.5 microg and 5 microg/50 microL) on mechanically evoked responses of dorsal horn neurons in anaesthetized Sprague-Dawley rats were studied. Intraplantar injection of the higher dose of NADA (5 microg/50 microL) studied significantly inhibited innocuous (8, 10 g) mechanically evoked responses of dorsal horn neurons compared to vehicle, effects blocked by intraplantar injection of SR141716A. Higher weight (26-100 g) noxious-evoked responses of dorsal horn neurons were also significantly inhibited by NADA (5 microg/50 microL), effects blocked by intraplantar injection of the TRPV1 antagonist, iodo-resiniferatoxin. NADA has a complex pattern of effects on DRG neurons and primary afferent fibres, which is likely to reflect its dual site of action at TRPV1 and CB(1) receptors and the differential expression of these receptors by primary afferent fibres.     

Physical status of newborns and neonatal outcome

OBJECTIVE: To determine the extent to which physical status at birth is associated with neonatal mortality and the causes of mortality vis-a-vis size at birth and gestational age. METHOD: 11,223 consecutive live births completing 26 weeks of gestation and weighing > or = 500 gm were included in the study. Birth weight and chest circumference were recorded as per WHO guidelines. Gestational age was calculated on the basis of L.M.P. and the new Ballard's score. Deaths occurring in the hospital within 28 days were recorded. Percentile values of gestational age specific birth weights were calculated separately for singletons and multiple births. Percentage of SGA was calculated with reference to WHO recommended values. Birth weight-gestational age-specific mortality rates were calculated at 2 wk and 500 gm intervals. RESULT: Low-birth-weight babies constituted 39.8% of the total, much in excess of WHO recommended figure of 15%. 76% deaths occurred among LBW babies and 56.2% among preterms. Mortality showed remarkable decline as the birth weight increased to 2,000 gm. The lowest mortality was among singletons weighing 2,500-3,000 gm and of 38-40 weeks gestation. Prevalence of SGA at 40 and 42 weeks were 73.7% and 83.6% respectively. But, if SGA babies not categorised as LBW were excluded, the values came down to 32% and 36% respectively. 36% of all deaths occurred during the first 24 hrs of birth; asphyxia and related causes contributing to 50% of it. CONCLUSION: Cut-off value of 2,000 gm instead of 2,500 gm for birth weight may be preferable in countries where most LBW babies are SGAs. Simultaneously, deaths in non-LBW babies due to perinatal causes contribute sgnificantly to total neonatal mortality and need due attention through sensitising obstetricians in essential newbom care and timely Intervention.     

Haemangioma calcificans

Haemangioma calcificans is a relatively rare intracranial tumour, which is characterized by the presence of a calcified nodule in or near the brain. The patient is most often an adult of either sex, who develops seizures. The lesion can be large enough to produce raised intracranial pressure. The location of tumour is subcortical and often in the temporal lobe. It is usually solitary and benign in nature. Microscopically, there are thin-walled blood vessels separated by dense fibrous bands containing deposits of haemosiderin and calcium. On electron microscopy, tubular structures limited by a wall of electrodense material and irregular calcium deposits within them are prominent features. Four cases of haemangioma calcificans are described here with review of literature.     

Pharmacokinetic evaluation of guar gum-based colon-targeted drug delivery systems of tinidazole in healthy human volunteers

The aim of the present investigation was to determine the in vivo availability of guar gum-based colon-targeted tablets of tinidazole in comparison with immediate release tablets of tinidazole in human volunteers. Six healthy volunteers participated in the study, and a cross-over design was used. The plasma concentration of tinidazole was estimated by HPLC. The pharmacokinetic parameters were calculated from the plasma concentration of tinidazole versus time data. The immediate release tablets of tinidazole produced a peak plasma concentration (C_max of 3239 ± 428 ng/ml) at 1.04 ± 0.32 hr (T_max), whereas colon-targeted tablets produced peak plasma concentration (C_max of 2158 ± 78 ng/ml) at 14.9 ± 1.6 hr. The delayed T_max, decreased C_max, and K_a, and unaltered bioavailability and elimination half-life of tinidazole from guar gum-based colon-targeted tinidazole tablets, in comparison with the immediate tablets, indicated that the drug was not released in the stomach and small intestine but delivered to the colon. Slow absorption of the drug from the less absorptive colon might result in the availability of the drug for local action in the colon. The guar gum-based colon-targeted tablets of tinidazole may be useful in providing an effective and safe therapy of intestinal amoebiasis.     

Antinociceptive and hypnotic effects of Premna tomentosa L. (Verbenaceae) in experimental animals

Medicinal plants are believed to be an important source of new chemical substances with potential therapeutic effects. The research into plants with alleged folklore use as pain relievers should therefore be viewed as a fruitful and logical research strategy in the search of new analgesic drugs. In the present inquiry, antinociceptive effects of Premna tomentosa (PT) leaf extract (in methanol) were explored in experimental animals by acetic acid-induced writhing, tail flick and tail clip tests. Oral administration of PT extract at different doses (100, 200, 400 and 500 mg/kg) led to significant antinociceptive effects. The extract was also tested for hypnotic effects. Treatment with extracts at different doses (100, 200, 400 and 500 mg/kg) decreased the locomotor activity and potentiated the pentobarbitone-induced sleep time. The responses were dose-dependent. On the basis of the present finding, we can conclude that PT possesses antinociceptive and hypnotic activities.