Treatment of pathologic spinal fractures with combined radiofrequency ablation and balloon kyphoplasty

Background

A current paradigm in the treatment of cervical cancer with radiation therapy is that intracavitary brachytherapy is an essential component of radical treatment. This is a matched retrospective comparison of the results of treatment in patients treated with external beam chemoradiation (EBRT-CT) and radical hysterectomy versus those treated with identical chemoradiation followed by brachytherapy.

Methods

In this non-randomized comparison EBRT-CT protocol was the same in both groups of 40 patients. In the standard treated patients, EBRT-CT was followed by one or two intracavitary Cesium (low-dose rate) applications within 2 weeks of finishing external radiation to reach a point A dose of at least 85 Gy. In the surgically treated patients, radical hysterectomy with bilateral pelvic lymph node dissection and para-aortic lymph node sampling were performed within 7 weeks after EBRT-CT. Response, toxicity and survival were evaluated.

Results

A total of 80 patients were analyzed. The patients receiving EBRT-CT and surgery were matched with the standard treated cases. There were no differences in the clinicopathological characteristics between groups or in the delivery of EBRT-CT. The pattern of acute and late toxicity differed. Standard treated patients had more chronic proctitis while the surgically treated had acute complications of surgery and hydronephrosis. At a maximum follow-up of 60 months, median follow-up 26 (2–31) and 22 (3–27) months for the surgery and standard therapy respectively, eight patients per group have recurred and died. The progression free and overall survival are the same in both groups.

Conclusion

The results of this study suggest that radical hysterectomy can be used after EBRT-CT without compromising survival in FIGO stage IB2-IIB cervical cancer patients in settings were brachytherapy is not available. A randomized study is needed to uncover the value of surgery after EBRT-CT.     

Cashmirols A and B,New Lipoxygenase Inhibiting Triterpenes from Sorbus cashmiriana

Two new triterpenes, cashmirols A and B ( 1 and 2 , resp.), along with three known compounds have been isolated from the AcOEt‐soluble fraction of Sorbus cashmiriana, and their structures were elucidated by spectroscopic techniques including two‐dimensional NMR. Both compounds displayed lipoxygenase enzyme inhibitory potential.     

Sulfide Oxidation Coupled to Arsenate Reduction by a Diverse Microbial Community in a Soda Lake

We characterized the arsenate-reducing, sulfide-oxidizing population of Mono Lake, California, by analyzing the distribution and diversity of rrnA, cbbL, and dissimilatory arsenate reductase (arrA) genes in environmental DNA, arsenate-plus sulfide-amended lake water, mixed cultures, and isolates. The arsenate-reducing community was diverse. An organism represented by an rrnA sequence previously retrieved from Mono Lake and affiliated with the Desulfobulbaceae (Deltaproteobacteria) appears to be an important member of the arsenate-reducing, sulfide-oxidizing community. Sulfide oxidation coupled with arsenate reduction appears to proceed via a two-electron transfer, resulting in the production of arsenite and an intermediate S compound that is subsequently disproportionated. A realgar-like As/S mineral was formed in some experiments.     

Studies on low molecular mass phytocystatins purified from Phaseolus mungo (Urd)

In the present study two phytocystatins (thiol protease inhibitors) have been isolated and purified to homogeneity from Phaseolus mungo by a simple two-step procedure using ammonium sulfate fractionation and gel filtration on Sephacryl-100 HR. The latter procedure yielded two peaks of the inhibitors (PMC I and PMC II). The pH optimum of both phytocystatins was pH 7.0; the temperature optima for PMC I and PMC II were 65 and 70 degrees C, respectively. The molecular masses of the purified phytocystatins were 19 and 17 kD, respectively, as determined by SDS-PAGE and mass spectrometry. Antibodies raised against the purified cystatins gave a single precipitin line in Ouchterlony double immunodiffusion. Kinetics of inhibition showed that PMC I and PMC II strongly inhibit papain and ficin but not trypsin and chymotrypsin. Binding stoichiometry of PMC I and PMC II with both papain and ficin was 1 : 2. The effect of urea on PMC I and PMC II was analyzed by fluorescence and circular dichroism spectroscopy. The CD results suggest an unfolding of PMC I and PMC II accompanying a decrease in the amount of extended (hydrated) coil structure and an increase in sheet-like structure. FTIR results show that PMC I is structurally similar to PMC II. Hydrophobic interactions are observed over a long time scale (5-150 min). Furthermore, fluorescence spectroscopy results were found to be in accordance with CD results, by showing quenching of fluorescence intensity of PMC I and PMC II, although to different extents, due to perturbations of the environment of aromatic residues in the protein. Both cystatins showed strong inhibitory activity against Escherichia coli and Staphylococcus aureus.     

Biochemical effects of Nigella sativa L seeds in diabetic rats

Oral administration of ethanol extract of N. sativa seeds (300 mg/kg body weight/day) to streptozotocin induced diabetic rats for 30 days significantly reduced the elevated levels of blood glucose, lipids, plasma insulin and improved altered levels of lipid peroxidation products (TBARS and hydroperoxides) and antioxidant enzymes like catalase, superoxide dismutase, reduced glutathione and glutathione peroxidase in liver and kidney. The results confirm the antidiabetic activity of N. sativa seeds extract and suggest that because of its antioxidant effects its administration may be useful in controlling the diabetic complications in experimental diabetic rats.     

Insight into the biochemical characterization of phytocystatin from Glycine max and its interaction with Cd+2 and Ni+2

Phytocystatins are cysteine proteinase inhibitors ubiquitously present in plants and animals. They are known to carry out various significant physiological functions and also maintain the balance of protease‐antiprotease activity. In the present disquisition, a phytocystatin after preliminary treatment has been isolated and purified to homogeneity from soybean (Glycine max) by a simple two‐step stratagem using ammonium sulfate fractionation and gel filtration chromatography performed on Sephacryl S‐100‐HR. Soybean phytocystatin (SBPC) was purified with a fold purification of 635 and percent yield of 77.6%. A single band was observed on native gel electrophoresis confirming the homogeneity of the purified SBPC. The molecular weight of SBPC was found to be 19.05 kDa as determined by SDS‐PAGE. The SBPC was found to be devoid of carbohydrate moieties and sulfhydryl group content. The binding stoichiometry of SBPC‐papain interaction was determined by isothermal calorimetry suggesting 1:1 complex, and the value of binding constant (K) was found to be 2.78 × 10⁵ M^?1 The affinity of binding (K_d) value obtained through ITC was 3.59 × 10^?6 M. The purified SBPC was found to be stable in the pH range of 3 to 7 and is thermostable up to 50°C. The UV‐visible and fluorescence studies showed significant changes in the conformation upon the formation of the SBPC‐papain complex. Furthermore, fluorescence spectroscopy, ANS binding, and caseinolytic activity assay were conducted out to explore the effect of metal ions on SBPC which showed that there was a loss in the inhibitory activity along with conformational changes of SBPC upon complex formation with Cd⁺² and Ni⁺².     

Spectroscopic studies on the interaction of bilirubin with liver cystatin

Studies on the role of endogenous metabolites such as bilirubin and their interactions with biomolecules have attracted considerable attention over the past several years. In this work, the interaction of bilirubin (BR) with purified goat liver cystatin (LC) was studied using fluorescence and ultraviolet (UV) spectroscopy. The fluorescence data proved that the fluorescence quenching of liver cystatin by BR was the result of BR–cystatin complex formation. Stern–Volmer analysis of fluorescence quenching data showed the binding constant to be 9.27 × 10⁴ M⁻¹ and the number of binding sites to be close to unity. The conformation of the BR–cystatin complex was found to change upon varying the pH of the complex. The BR–cystatin complex was found to have reduced papain inhibitory activity. Photo-illumination of BR–cystatin complex causes perturbation in the micro-environment of goat liver cystatin as indicated by red-shift. This report summarizes our research efforts to reveal the mechanism of interaction of bilirubin with liver cystatin.     

Geographic Variation in Access to Dog-Bite Care in Pakistan and Risk of Dog-Bite Exposure in Karachi: Prospective Surveillance Using a Low-Cost Mobile Phone System

Background

Dog-bites and rabies are under-reported in developing countries such as Pakistan and there is a poor understanding of the disease burden. We prospectively collected data utilizing mobile phones for dog-bite and rabies surveillance across nine emergency rooms (ER) in Pakistan, recording patient health-seeking behaviors, access to care and analyzed spatial distribution of cases from Karachi.

Methodology and Principal Findings

A total of 6212 dog-bite cases were identified over two years starting in February 2009 with largest number reported from Karachi (59.7%), followed by Peshawar (13.1%) and Hyderabad (11.4%). Severity of dog-bites was assessed using the WHO classification. Forty percent of patients had Category I (least severe) bites, 28.1% had Category II bites and 31.9% had Category III (most severe bites). Patients visiting a large public hospital ER in Karachi were least likely to seek immediate healthcare at non-medical facilities (Odds Ratio = 0.20, 95% CI 0.17–0.23, p-value<0.01), and had shorter mean travel time to emergency rooms, adjusted for age and gender (32.78 min, 95% CI 31.82–33.78, p-value<0.01) than patients visiting hospitals in smaller cities. Spatial analysis of dog-bites in Karachi suggested clustering of cases (Moran''s I = 0.02, p value<0.01), and increased risk of exposure in particular around Korangi and Malir that are adjacent to the city''s largest abattoir in Landhi. The direct cost of operating the mHealth surveillance system was USD 7.15 per dog-bite case reported, or approximately USD 44,408 over two years.

Conclusions

Our findings suggest significant differences in access to care and health-seeking behaviors in Pakistan following dog-bites. The distribution of cases in Karachi was suggestive of clustering of cases that could guide targeted disease-control efforts in the city. Mobile phone technologies for health (mHealth) allowed for the operation of a national-level disease reporting and surveillance system at a low cost.     

Human genetic polymorphisms in T1R1 and T1R3 taste receptor subunits affect their function

Umami is the typical taste induced by monosodium glutamate (MSG), which is thought to be detected by the heterodimeric G protein-coupled receptor, T1R1 and T1R3. Previously, we showed that MSG detection thresholds differ substantially between individuals and we further showed that nontaster and hypotaster subjects are associated with nonsynonymous single polymorphisms occurring in the T1R1 and T1R3 genes. Here, we show using functional expression that both amino acid substitutions (A110V and R507Q) in the N-terminal ligand-binding domain of T1R1 and the 2 other ones (F749S and R757C), located in the transmembrane domain of T1R3, severely impair in vitro T1R1/T1R3 response to MSG. A molecular model of the ligand-binding region of T1R1/T1R3 provides a mechanistic explanation supporting functional expression data. The data presented here support causal relations between the genotype and previous in vivo psychophysical studies in human evaluating sensitivity to MSG.     

Plasmodium salvages cholesterol internalized by LDL and synthesized de novo in the liver

Our previous morphological studies illustrated the association of sterols with Plasmodium infecting hepatocytes. Because malaria parasites cannot synthesize sterols, they must scavenge these lipids from the host. In this paper, we have examined the source/s of sterols for intrahepatic Plasmodium and evaluated the importance of sterols for liver stage development. We show that Plasmodium continuously diverts cholesterol from hepatocytes until release of merozoites. Removal of plasma lipoproteins from the medium results in a 70% reduction of cholesterol content in hepatic merozoites but these parasites remain infectious in animals. Plasmodium salvages cholesterol that has been internalized by low-density lipoprotein but reduced expression of host low-density lipoprotein receptors by 70% does not influence liver stage burden. Plasmodium is also able to intercept cholesterol synthesized by hepatocytes. Pharmacological blockade of host squalene synthase or downregulation of the expression of this enzyme by 80% decreases by twofold the cholesterol content of merozoites without further impacting parasite development. These data enlighten that, on one hand, malaria parasites have moderate need of sterols for optimal development in hepatocytes and, on the other hand, they can adapt to survive in cholesterol-restrictive conditions by exploitation of accessible sterols derived from alternative sources in hepatocytes to maintain proper infectivity.