Vitamin B6 metabolites in idiopathic calcium stone formers: no evidence for a link to hyperoxaluria

Vitamin B6 metabolites and their potential correlates to urinary oxalate excretion in idiopathic calcium stone formers (ICSF) compared with healthy subjects were investigated. This clinical study was performed in a population of male ICSF with (Hyperoxalurics, n=55) or without hyperoxaluria (Normooxalurics, n=57) as well as in 100 healthy male control subjects. Pyridoxal 5-phosphate serum concentration (S-pyridoxal 5P) and 24-h urinary excretion of 4-pyridoxic acid (U-4pyridoxic acid) were measured using HPLC; 24-h urinary excretion of oxalate (U-oxalate) was measured concurrently. A subgroup of subjects (40 Hyperoxalurics, 15 Normooxalurics and 50 controls) underwent the same measurements before and after 7-day pyridoxine loading per os (pyridoxine hydrochloride, 300 mg/d). Under usual conditions, U-4pyridoxic acid was similar in the three groups, whereas mean S-pyridoxal 5P was significantly lower (p<0.0001) in the Hyperoxalurics (59.6±21.2 nmol/L) and in the Normooxalurics (64.9±19.7 nmol/L) than in the controls (86.0±31.0 nmol/L). No correlation could be found between U-oxalate and U-4pyridoxic acid or S-pyridoxal 5P. After B6 loading, S-pyridoxal 5P was still significantly lower in the Hyperoxalurics (415±180 nmol/L, p<0.001) and in the Normooxalurics (429±115 nmol/L, p=0.036) than in the controls (546±180 nmol/L), although there was no difference between groups for U-4pyridoxic acid. No correlation in any group could be found between changes in U-oxalate and changes in U-4pyridoxic acid or S-pyridoxal 5P. Although there is no vitamin B6 deficiency in ICSF with or without hyperoxaluria, these patients, on average, have lower levels of S-pyridoxal 5P than healthy subjects. However, this slight decrease does not seem to account for idiopathic hyperoxaluria.     

Rare case of congenital transsphenoidal meningoencephalocele causing respiratory problems

INTRODUCTION: Congenital meningoencephalocele is a rare and severe malformation. AIMS: The authors describe the case of congenital, basal transsphenoidal meningoencephalocele associated with other neurological malformations, which projected between the margins of palatoschisis producing respiratory problems at neonatal age. METHOD: Presented with detailed photo-documentation. RESULTS: Cranial meningoencephalocele reconstruction with an approach of bifrontal craniotomy was performed. The base of skull was closed multilaminarly with auto-graft gained from parietal bone and Lyodura. The closure of nasopharyngeal sac was performed in second sitting. Postoperatively the progression of hydrocephalus was so extensive, that implantation of ventriculo-peritoneal shunt was unavoidable. Later on closure of tracheotomy performed for continued air passage support was done. The authors report the course of disease and the surgeries performed. CONCLUSIONS: Auto-graft from skull bone for closure of large basal-cranial defect proved to be ideal. Prognosis depends on other malformations. Successful treatment needs co-operation of different specialties.     

Phenotypic variants of A3243G mitochondrial DNA mutation in a Hungarian family

The first Hungarian case with typical features of mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes (MELAS) in a young girl is presented. MELAS is a multisystem disorder inherited by the mitochondrial DNA with onset typically in childhood. Our patient presented the first symptoms at the age of 6 years with recurrent vomiting, nausea and transient visual loss. Several stroke-like episodes followed gradually impairing motor abilities and mental development. Molecular analysis of the mitochondrial DNA confirmed a heteroplasmic A3243G transition. The maternal family members were also tested for the mutation in peripheral blood DNA. In the mother of the proband, who suffers from bilateral hypacusis the mutation was detected in 20% of heteroplasmy, while in one of her asymptomatic sisters the mutation was present in 10% only. The bilateral hypacusis of the mother may be associated with this mutation and seems to differentiate the pedigree reported here from others published in the literature.     

Epidemiologic study of the psychological health and risk behaviors of medical students

INTRODUCTION AND AIMS: In the present study the authors conducted a cross sectional study of fourth-year (eighth-semester) students at Semmelweis University, to assess their stress-related complaints, and also some of the more common forms of risk behavior, including smoking, regular alcohol consumption, past or current drug use and the regular use of pharmaceuticals. METHODS: A total of 410 students were evaluated; 263 medical students, 96 pharmaceutical students and 78 dentistry students. An adapted version of Anderson's questionnaire was used for the evaluation of the total burden of stress based on emotional, physical and work-related complaints. Respondents who mentioned more than three signs of increased stress involving any of the above three categories (emotional, physical and work-related) were designated "high risk" subjects. RESULTS: The overall prevalence of "high risk" subjects was 30.5% (29.7% in medical, 38.5% in pharmaceutical and 23.1% in dentistry students) with no significant gender differences. 55.2% of "high risk" subjects had over three complaints in only one category, 32.6% in two categories, and 12.2% in all three categories. 43.6% of the subjects experienced work-related complaints, 33.3% of them had emotional and 23.1% had physical complaints. The overall prevalence of various forms of risk behavior was found to be 19.3% for smoking (25.2% in males and 15% in females), 30.2% for regular alcohol intake (47.1 in males and 18.3% in females), 25.4% for the regular use of some kind of medication (14.7% in males and 33.0% in females) and 24.9% for those who admitted to previous drug-use (37.6% in males and 16.3% in females). CONCLUSION: All forms of risk behavior were more common in the "high risk" group, but only smoking and the regular use of medication were increased significantly. There were no differences in risk behavior prevalence with regards to a particular category of complaints.     

Development of insulin resistance by nitrate tolerance in conscious rabbits

Clinical evidence has been raised to suggest that transdermal nitroglycerin increases the sensitivity of peripheral tissues to the hypoglycemic effect of insulin. In this study we determined whether development of tolerance to the hypotensive effect of nitroglycerin also resulted in tolerance to the insulin-sensitizing effect in rabbits. Intravenous glucose disposal and hyperinsulinemic euglycemic glucose clamp studies were performed on naive and hemodynamic nitrate tolerant conscious New Zealand white rabbits. These rabbits were exposed to continuous "patch on" with nitroglycerin (0.07 mg/kg/h) or placebo patches over 7 days. Nitroglycerin treatment of 7 days produced a lack of hypotensive response to a single intravenous bolus of 30 microg/kg nitroglycerin, which caused a significant decrease in mean arterial blood pressure in control rabbits. A six-hour exposure to transdermal nitroglycerin significantly increased insulin sensitivity determined by hyperinsulinemic (100 microU/ml) euglycemic (5.5 mmol/l) glucose clamping as compared with that seen in rabbits treated with placebo patches. A significant decrease in insulin sensitivity was observed in the nitroglycerin patch-treated animals both in the presence and after the removal of the last patch when the patches were applied over 7 days. We conclude that acutely nitrate patches improve insulin sensitivity whereas a 7-day chronic treatment schedule that results in hemodynamic nitrate tolerance also produces insulin resistance.     

Crystal structures of the mitochondrial deoxyribonucleotidase in complex with two specific inhibitors

Monophosphate nucleotidases are enzymes that dephosphorylate nucleotides to their corresponding nucleosides. They play potentially important roles in controlling the activation of nucleotide-based drugs targeted against viral infections or cancer cells. The human mitochondrial deoxyribonucleotidase (dNT-2) dephosphorylates thymidine and deoxyuridine monophosphates. We describe the high resolution structures of the dNT-2 enzyme in complex with two potent nucleoside phosphonate inhibitors, (S)-1-[2'-deoxy-3',5'-O-(1-phosphono) benzylidene-beta-d-threo-pentofuranosyl]thymine (DPB-T) at 1.6-A resolution and (+/-)-1-trans-(2-phosphonomethoxycyclopentyl)uracil (PMcP-U) at 1.4-A resolution. The mixed competitive inhibitor DPB-T and the competitive inhibitor PMcP-U both bind in the active site of dNT-2 but in distinctly different binding modes, explaining their different kinetics of inhibition. The pyrimidine part of the inhibitors binds with very similar hydrogen bond interactions to the protein but with their phosphonate moieties in different binding sites compared with each other and to the previously determined position of phosphate bound to dNT-2. Together, these phosphate/phosphonate binding sites describe what might constitute a functionally relevant phosphate entrance tunnel to the active site. The structures of the inhibitors in complex with dNT-2, being the first such complexes of any nucleotidase, might provide important information for the design of more specific inhibitors to control the activation of nucleotide-based drugs.     

A comparison between single- and double-breath vital capacity inhalation induction with 8% sevoflurane in children

BACKGROUND: This study was conducted to determine if a double-breath (DB) vital capacity (VC) rapid inhalation induction using immediate high-inspired concentration of sevoflurane is as well tolerated as a single-breath (SB) technique and if it results in a shorter induction time. METHODS: A total of 104 children, ASA I-II, 6 year and above, undergoing elective surgery were randomly assigned to two groups: SB VC inhalation induction or DB VC inhalation induction with 8% sevoflurane in 66% nitrous oxide. The induction time, complications (cough, laryngospasm, breath-hold, movement, salivation) and level of satisfaction were documented. RESULTS: Induction was significantly faster in the DB group (41 +/- 9 s) compared with the SB group (50 +/- 14 s). DB inhalation induction was associated with fewer complications (15.4%) than the SB technique (50%). CONCLUSIONS: Double-breath VC inhalation induction with 8% sevoflurane is as well tolerated as a SB technique and results in a faster onset of anaesthesia.