Therapeutic potential of monoisoamyl and monomethyl esters of meso 2,3-dimercaptosuccinic acid in gallium arsenide intoxicated rats

The dose dependent effects of monoisoamyl and monomethyl esters of meso 2,3-dimercaptosuccinic acid (DMSA) (0.1, 0.3 and 0.5 mmol kg(-1), intraperitoneally (i.p.) once daily for 5 days) to offset the characteristic biochemical, immunological, oxidative stress consequences and DNA damage (based on DNA fragmentation and comet assay) following sub-chronic administration of gallium arsenide and the mobilization of gallium and arsenic were examined. The effects of these chelators alone in normal animals too were examined on above-mentioned variables. Male Wistar rats were exposed to 10 mg kg(-1), GaAs, orally once daily for 12 weeks and were administered DMSA or two of its monoesters (monoisoamyl or monomethyl) for 5 consecutive days. DMSA was used as a positive control. DMSA and its derivatives, when given alone, generally have no adverse effects on various parameters. After 5 days of chelation therapy in GaAs pre-exposed rats, MiADMSA was most effective in the reduction of inhibited blood delta-aminolevulinic acid dehydratase (ALAD) activity and zinc protoporphyrin level while, all three chelators effectively reduced urinary ALA excretion, compared to GaAs alone exposed rats. MiADMSA was also effective, particularly at a dose of 0.3 mmol kg(-1), in enhancing the inhibited hepatic transaminase activities. Parameters indicative of oxidative stress responded less favorably to the chelation therapy, however, three chelators significantly restored the altered immunological variables. MiADMSA was relatively more effective than the other two chelators. GaAs produced significant DNA damage in the liver and kidneys and the chelation treatment had moderate but significant influence in reducing DNA damage. All three chelators significantly reduced arsenic concentration and, however, MiADMSA was more effective than the other two chelators in depleting arsenic concentration from blood and other soft tissues. A dose of 0.3 mmol kg(-1) was found to be relatively better than the other two doses examined. Gallium contents of blood and soft tissues remained uninfluenced by the chelation therapy. Significant loss of copper after MiADMSA administration, however, is of concern and requires further exploration. Additionally, further studies are required for the choice of appropriate dose, duration of treatment and possible toxic/side effects. Keeping in view the promising role of MiADMSA in the treatment of GaAs poisoning, these data will be needed for the registration of this chelating agent as licensed drug for the treatment of gallium arsenide intoxication.     

Nutritional status of obese hypercholesterolemic adults

The study was conducted to collect information regarding food and nutrient intake of hypercholesterolemic adults (male n = 30, female n = 20). The Body Mass Index (BMI) of the respondents indicated that 70% of them had a BMI more than 26. The food intake of the respondents was recorded for three consecutive days using 24 hour dietary recall and questionnaire method. The intake of cereals, sugar and oil was significantly higher than the Recommended Dietary Intake (RDI) prescribed for Indians, whereas intake of pulses was at par with RDI. The consumption of green leafy and other vegetable and roots and tubers was significantly lower among both male and female respondents. The intake of protein was at par with recommended dietary allowance (RDA), but fat and energy intake were significantly higher in both male and female respondents. The subjects were given diet counselling and this received a good response from the respondents.     

Profiles of polychlorinated biphenyl congeners, organochlorine pesticides, and butyltins in southern sea otters and their prey

Concentrations of organochlorine pesticides, polychlorinated biphenyl (PCB) congeners, and butyltins were measured in sea otters and selected prey species (invertebrates) collected from the California (USA) coast. Polychlorinated biphenyls, DDTs (sum of p,p'-dichlorodiphenyldichloroethylene [p,p'-DDE], p,p'-dichlorodiphenyldichloroethane [p,p'-DDD], and p,p'-DDT), and butyltins were the major contaminants found in sea otters and their prey. Lipid-normalized concentrations of PCBs and DDT in sea otter livers were 60- and 240-fold greater than those found in the prey. Great biomagnification of PCBs and DDT in sea otters is suggested to result from their high per-capita intake of diet compared with those of other marine mammals. Profiles of PCB congeners in sea otters and prey species suggest a great capacity of sea otters to biotransform lower-chlorinated congeners. Sea otters seem to possess a greater ability than cetaceans to metabolize PCBs. The 2,3,7,8-tetrachlorodibenzo-p-dioxin equivalents of non- and mono-ortho PCBs in sea otters and certain prey species were at or above the theoretical threshold for toxic effects.     

Neonatal thrombosis

Neonatal thrombosis is a serious event that can cause mortality or result in severe morbidity and disability. The most important risk factor for the development of thrombosis during the neonatal period is the presence of an indwelling central line and consequently the vessels involved tend to be those most frequently used for catheterization. Other documented risk factors for the development of neonatal thrombosis include asphyxia, septicemia, dehydration, maternal diabetes and cardiac disease. Main laboratory findings for the diagnosis of hypercoagulable states, include shortened aPTT, decreased levels of inhibitors (AT III, Protein C and Protein S), increased resistance to activated protein C, defective fibrinolysis (basal and after stimuli), increased levels of clotting factors (fibrinogen, factor VII, factor VIII, etc.), increased and/or hyperactive platelets, increased whole blood and/or plasma viscosity, Antiphospholipid antibodies and presence of prothrombotic molecular defects like FV Leiden, P20210 and MTHFR. Approximately 4% and 2% respectively of Caucasians are heterozygous for these gene defects. Their causative role in neonatal thrombosis is unknown but they may have a contributory role in the pathogenesis of thrombosis in neonates.     

Desmoid tumour of the neck: complete regression following radiation therapy

Desmoid tumours are uncommon benign neoplasms. They arise from fascial and musculoaponeurotic tissues and are locally infiltrative, resulting in a high rate of local recurrence following surgical resection. They present difficult loco-regional control. The location and extent of the tumour, as well as the potential for significant morbidity and mortality, dictate the most appropriate therapeutic option. Complete surgical extirpation is the optimal treatment for primary and recurrent desmoid tumours. Radiotherapy is indicated in incompletely excised or recurrent tumours. Radiation as a primary treatment is seldom recommended. A case of desmoid tumour of the neck, primarily treated with radical radiation, is described and relevant literature reviewed.     

Propofol for pediatric radiotherapy

Objective : Pediatric radiotherapy is a day care procedure. In children, anaesthesia is necessary to prevent movement during the therapy. Traditionally intramuscular ketamine is used for these procedure because of its inherent safety in a child who used to be left alone in the cobalt room.Methods : This study was designed to explore the efficacy of propofol and ketamine in pediatric radiotherapy in nineteen children. The inclusion criteria was a child fasting for six hours with no fever or URTI in the past week. A child coming to the radiotherapy (RT) unit without an intravenous cannula was given intramuscular ketamine 10 mg/kg and taken for the procedure. Before the child recovered from anaesthesia an intravenous cannula, 20–22G, Vasofix was inserted for subsequent sittings of RT. The child coming with an intravenous cannula was given propofol 2.5 mg/kg with xylocaine (0.1 mg/kg) without adrenaline. The parameters recorded were pulse rate, oxygen saturation and respiratory rate-baseline to every 30 seconds till five minutes. Onset time, recovery time, oral feeding time and any untoward effects like nausea, vomiting, nystagmus were also noted.Result: The drug was graded on a scale of 0–10 according to parental acceptability where 0 is the worst and 10 is the best acceptability. The mean (±SD) of all the measured parameters were calculated and compared between the two groups.Conclusion : Propofol was associated with faster onset, better recovery, early oral feeding time, no nausea and vomiting and better parental acceptability. There was no hypotension, bradycardia and oxygen saturation at 60 seconds, which was betwen 94–95%, was easily treatable with supplementation of oxygen by face mask     

Ran's C-terminal,basic patch,and nucleotide exchange mechanisms in light of a canonical structure for Rab,Rho, Ras,and Ran GTPases

Proteins comprising the core of the eukaryotic cellular machinery are often highly conserved, presumably due to selective constraints maintaining important structural features. We have developed statistical procedures to decompose these constraints into distinct categories and to pinpoint critical structural features within each category. When applied to P-loop GTPases, this revealed within Rab, Rho, Ras, and Ran a canonical network of molecular interactions centered on bound nucleotide. This network presumably performs a crucial structural and/or mechanistic role considering that it has persisted for more than a billion years after the divergence of these families. We call these 'FY-pivot' GTPases after their most distinguishing feature, a phenylalanine or tyrosine that functions as a pivot within this network. Specific families deviate somewhat from canonical features in interesting ways, presumably reflecting their functional specialization during evolution. We illustrate this here for Ran GTPases, within which two highly conserved histidines, His30 and His139, strikingly diverge from their canonical counterparts. These, along with other residues specifically conserved in Ran, such as Tyr98, Lys99, and Phe138, appear to work in conjunction with FY-pivot canonical residues to facilitate alternative conformations in which these histidines are strategically positioned to couple Ran's basic patch and C-terminal switch to nucleotide exchange and effector binding. Other core components of the cellular machinery are likewise amenable to this approach, which we term Contrast Hierarchical Alignment and Interaction Network (CHAIN) analysis.     

Concealed penis

A small phallus causes great concern regarding genital adequacy. A concealed penis, although of normal size, appears small either because it is buried in prepubic tissues, enclosed in scrotal tissue penis palmatus (PP), or trapped due to phimosis or a scar following circumcision or trauma. From July 1978 to January 2001 we operated upon 92 boys with concealed penises; 49 had buried penises (BP), while PP of varying degrees was noted in 14. Of 29 patients with a trapped penis, phimosis was noted in 9, post-circumcision cicatrix (PCC) in 17, radical circumcision in 2, and posttraumatic scarring in 1. The BP was corrected at 2-3 years of age by incising the inner prepuce circumferentially, degloving the penis to the penopubic junction, dividing dysgenetic bands, and suturing the dermis of the penopubic skin to Buck's fascia with nonabsorbable sutures. Patients with PP required displacement of the scrotum in addition to correction of the BP. Phimosis was treated by circumcision. Patients with a PCC were recircumcised carefully, preserving normal skin, but Z-plasties and Byars flaps were often required for skin coverage. After radical circumcision and trauma, vascularized flaps were raised to cover the defect. Satisfactory results were obtained in all cases although 2 patients with BP required a second operation. The operation required to correct a concealed penis has to be tailored to its etiology.