Lactate and Pyruvate Levels in the Testicular Vein of Subfertile Males with Varicocele as a Test for the Theory of Underlying Hypoxia

Lactat- und Pyruvat-Werte in der Vena testicularis von subfertilen Männern als Test für die Theorie der vorhandenen Hypoxie
Um die These von der testikulären Hypoxie bei subfertilen Männern mit Varikocele zu überprüfen wurden die Blutwerte von Lactat und Pyruvat aus der Vena testicularis mit denen einer Kontrollgruppe verglichen. Statistisch ergab sich ein niedrigerer Mittelwert für Lactat und Pyruvat bei den Varikocele-Patienten. Daraus wird die Schlußfolgerung gezogen, daß bei Varikocele keine Akkumulation von Milchsäure erfolgt und daß damit eine Hypoxie ausgeschlossen werden kann. Als die Mittelwerte der Konzentrationen für Lactat und Pyruvat in der Vena testicularis miteinander korreliert wurden, deutete sich an, daß bei Vorhandensein einer Varikocele eine gestörte Glykolyse besteht, die dem Stadium der Pyruvatbildung vorhergeht.     

Octylcyanoacrylate (Dermabond) for skin closure at the time of head and neck surgery: a longitudinal prospective study

OBJECTIVES: A prospective non-randomised evaluation of the octyl-2-cyanoacrylate (Dermabond) for skin closure in head and neck surgery. MATERIALS AND METHODS: An inception cohort of 52 patients managed by six otorhinolaryngologists head and neck surgeons at a single institution (university teaching and tertiary referral center) during the months of May-July 2004. The length of the skin incision varied from 3 to 30 cm (mean: 7 cm). Morbidity evaluation, longitudinal analysis of the evolution of the scar, and analysis of the degree of satisfaction. RESULTS: Postoperative death was not encountered. The overall morbidity rate was 3.8% (2/52). There was no instances of wound dehiscence's. A subcutaneous abscess was noted in one patient. From an aesthetic point of view, the scar appearance was considered to be slightly retracted during the first postoperative month and to be very good 2 to 4 months from initial surgery. Only one patient developed a minimal cheloid scar. Among the 47 patients who expressed an opinion postoperatively regarding the use of the octyl-2-cyanoacrylate (Dermabond) for skin closure, the degree of satisfaction was very high due to the ability to take an early shower (40 patients) followed by the lack of skin sutures (5 patients) and the lack of any allergic skin reaction (2 patients). CONCLUSION: At our department, the octyl-2-cyanoacrylate (Dermabond) for skin closure at the time of head and neck surgery is becoming more and more utilized due to the completion of a solid and aesthetic suture, the ability to take an early shower and the high degree of satisfaction expressed by the patients.     

Significant NK cell activation associated with decreased cytolytic function in peripheral blood of HIV-1-infected patients

One of the hallmarks of HIV-1 infection is represented by the finding of massive T cell activation in peripheral blood lymphocytes of infected patients. An impairment of NK cell function during HIV-1 infection is also detected, and is associated with decreased expression of natural cytotoxicity receptors (NCR). In this study we tried to determine whether also NK cells are affected by relevant activation and whether this could be associated with decreased NK cell function. In 18 viremic HIV-1-infected patients, freshly drawn purified peripheral NK cells displayed significant levels of activation with an incomplete pattern (HLA-DR(+)CD69(+)CD25(-)NKp44(-)). Activated (HLA-DR(+)CD69(+)) peripheral NK cells expressed an NCR(dull) phenotype as determined by cytofluorometric analysis in all the patients, and did not derive from a homogeneous/oligoclonal expansion in vivo as analyzed by expression of HLA-specific inhibitory NK cell receptors. As determined by cytotoxicity assays, activated NK cells showed a decreased cytolytic function in HIV-1-infected patients. Thus, the decrease in NK cell function observed during HIV-1 infection is associated not only with decreased NCR expression, but also with significant and incomplete NK cell activation in vivo. These results suggest a consistent continuous involvement of the innate immune response in the failure to control viral replication.     

Neoral dose adjustment after conversion from C0 to C2 monitoring in stable renal transplant recipients: a prospective single center study

To determine the clinical impact of conversion from C0 to C2 Neoral monitoring, we conducted a 6-month prospective study in 62 stable renal transplant recipients. Neoral was given alone (19%), with steroids (31%), combined with azathioprine (Aza) or mycophenolate mofetil (MMF) (50%). C0 and C2 target ranges were, respectively, 130-190 and 700-900 ng/mL. Neoral dosages were adjusted according to the C2 range. At baseline, mean C0 and C2 were 157 and 762 ng/mL. After 6 months C0 was 173 ng/mL (p<0.02) and C2 was 804 ng/mL (ns). Although the mean Neoral dose at 6 months was unchanged from baseline, the dose was reduced in 24 patients from 3.6+/-1.2 to 3.0+/-0.9 mg/kg/day, with a mean reduction in serum creatinine (Cr) from 1.4+/-0.4 to 1.3+/-0.3 mg/dL (p<0.001), stable in 8 patients and increased in 30 patients from 3.3+/-1.0 to 3.8+/-1.2 mg/kg/day with no change in serum Cr. Serum transaminases and blood pressure (BP) were unchanged in the three groups. C0 and C2 showed a positive correlation, but with a large dispersion of values (r2=0.14, p<0.001). Overall concordance between the C0 and C2 ranges was 49%. Therefore, in stable transplant patients C0 cannot be considered a C2 surrogate. The conversion from C0 to C2 led to a Neoral dose reduction in approximately 40% of patients with significant improvement in renal function. Most of the remaining patients required an increased dose; however, without an increased incidence of cyclosporin-induced side-effects.     

A novel class of nonpeptidic biaryl inhibitors of human cathepsin K

A novel series of nonpeptidic biaryl compounds was identified as potent and reversible inhibitors of cathepsin K. The P2-P3 amide bond of a known amino acetonitrile dipeptide 1 was replaced with a phenyl ring, thereby giving rise to this biaryl series that retained potency vs cathepsin K and showed an improved selectivity profile against other cathepsins. Structural modification within this series resulted in the identification of compound (R)-2, a potent human cathepsin K inhibitor (IC(50) = 3 nM) that is selective versus cathepsins B (IC(50) = 3950 nM), L (IC(50) = 3725 nM), and S (IC(50) = 2010 nM). In an in vitro assay involving rabbit osteoclasts and bovine bone, compound (R)-2 inhibited bone resorption with an IC(50) of 95 nM. It was shown that, unlike some peptidic nitrile inhibitors of cysteine proteases, the nitrile moiety of (R)-2 is not converted to the corresponding amide 3 by cathepsin K. This indicates that this class of nonpeptidic nitrile inhibitors is unlikely to be hydrolyzed by cysteine proteases. Furthermore, the inhibition of cathepsin K by compound (R)-2 was shown to be fully reversible and not observably time-dependent. To demonstrate the efficacy of compound (R)-2 in vivo, it was administered to ovariectomized (OVX) rhesus monkeys at 20 mg/kg, po once daily for 8 days, and a urinary marker of bone turnover, N-telopeptide of type I collagen (uNTx), was measured. During the eight-day dosing period, the mean reduction by compound (R)-2 in uNTx was 80% (p < 0.001). This demonstrates that inhibition of cathepsin K leads to an inhibition of this bone resorption marker in OVX rhesus monkeys and strongly suggests that inhibition of cathepsin K is a viable therapeutic approach for the treatment of osteoporosis.     

STUDIES ON THE SPASMOLYTIC AND UTERINE RELAXANT ACTIONS OF N -ETHYL AND N -BENZYL-1,2-DIPHENYL ETHANOLAMINES: ELUCIDATION OF THE MECHANISMS OF ACTION

The influence of N -ethyl- and N -benzyl-1,2-diphenyl ethanolamines (compounds E and B, respectively) was examined on the spontaneously contracting rabbit jejunum and the rat uterus together with their influence on the contractions induced by some spasmogens in the guinea-pig ileum and oxytocics and CaCl₂in the pregnant rat uterus. Both E and B inhibited the spontaneous contractions of the rabbit jejunum with ID₅₀values of 0.13 and 0.03 μmol ml⁻¹. Their inhibitory activities were not antagonized by α- or β-adrenoceptor blockers but significantly reversed by CaCl₂(0.015 μmol ml⁻¹). The compounds also antagonized nicotine, ACh-, histamine-, 5-HT- and CaCl₂-induced contractions by 44–100%. Compound E seemed to be several times more potent than B in inhibiting the spontaneous uterine contractions with an ID₅₀of (7 nmol ml⁻¹). Their inhibitory effects were not antagonized by β₂-adrenoceptor or H₂-receptor blocking drugs. Both compounds (40 nmol ml⁻¹) antagonized in a competitive manner CaCl₂-induced contractions in the K⁺-depolarised uterus and PGE₂and oxytocin-induced uterine contractions. The ID₅₀values were in the range of 1.6–10.7 nmol ml⁻¹. The results suggest that E and B compounds may be considered as putative L-Ca²⁺channel blockers with certain selectivities. The E compound seemed to be more selective against uterine L-Ca²⁺channels and the B compound against intestinal smooth muscles. Thus, the compounds may be of potential value in treatment of some colics, the irritant bowel syndrome, dysmenorrhoea and premature deliveries. 1999 Academic Press@p$hr     

The use of DNA markers for carrier detection and prenatal diagnosis of haemophilia A in Egyptian families

Summary. Haemophilia A is the most common inherited X‐linked recessive bleeding disorder. The aim was to investigate the usefulness of two DNA markers in linkage analysis, one intragenic BCL1 affecting restriction site in intron 18, and is detected as restriction fragment length polymorphism (RFLP), and one extragenic variable number of tandem repeat (VNTR) locus DXS52 (St14) to formulate an informative and accurate carrier detection and prenatal diagnosis. The study included 46 families with at least one child affected with haemophilia A, and 30 unrelated normal females as control group. Polymerase chain reaction (PCR) and restriction enzyme analysis were used to study the polymorphism in BCL1, and long‐distance PCR for detection of VNTR (ST14) alleles. The incidence of BCL1 (+) allele was 74%, 72% and 60% in patients, mothers and control group, respectively. Expected heterozygosity for BCL1 was 40% in mothers of affected cases compared with 48% in the female control group. However, observed heterozygosity was found to be 48% in the mothers of affected cases, compared with 60% in the control group. Thus, 48% of the studied families are informative for this marker alone. Nine different alleles of VNTR (St14) were observed in mothers and six alleles in affected cases and six in the control group. The most prevalent alleles were 1300 bp (45.5% and 34%) and 700 bp (13.6% and 20%) in patients and their mothers, respectively. Observed heterozygosity in mothers was 41% compared with 43.3% in controls. The combined use of both BCL1 and St14 markers raised the informative rate to 63.6%. Carrier detection and prenatal diagnosis is possible in haemophilia A families using both DNA markers. We suggest screening haemophilic families first for BCL1 polymorphism followed by analysis of St14 locus.