Congenital pseudarthrosis of the ulna

We report a case of congenital pseudarthrosis of the ulna along with generalized neurofibromatosis (type I). The patient had a good clinical outcome after single-bone forearm reconstruction. In the setting of radial head dislocation following long-standing congenital pseudarthrosis of the ulna, single-bone forearm reconstruction is a viable option. It prevents the loss of hand function by the effective shortening of flexor tendons and spares movements of the humeroulnar and radiocarpal joints.     

Association of folate with hearing is dependent on the 5,10-methylenetetrahdyrofolate reductase 677C-->T mutation

Vascular disease and its risk factors have been associated with the age-related hearing loss. We examined the association of elevated plasma homocysteine and its determinants with hearing levels. Pure-tone air conduction thresholds in 728 individuals with sensorineural hearing loss were not associated with homocysteine, erythrocyte folate and Vitamin B6. Low concentrations of serum folate and Vitamin B12 were associated with better hearing. When folate status was below the median, 5,10-methylenetetrahydrofolate reductase (MTHFR) 677TT homozygotes had similar hearing levels to subjects with a C allele. However, when folate status was above the median, MTHFR 677TT homozygotes had on an average 5 dB (p = 0.037) and 2.6 dB (p = 0.021) lower PTA-high and PTA-low hearing thresholds, respectively, than the subjects with a 677C allele. The relationship between serum folate and hearing thresholds appeared to be dependent on MTHFR 677 genotype (CC, r = 0.13, p = 0.034; TT, r = -0.10, p = 0.291). This supports the hypothesis that a greater one-carbon moiety commitment to de novo synthesis of nucleotides and an increase in formyl-folate derivatives relative to methyl-folate derivatives is protective for hearing.     

Protective effect of 2-hydroxy-4-methoxy benzoic acid on testosterone induced benign prostatic hyperplasia in Wister rats

Oxidative stress is one of the major causative factors for development of benign prostatic hyperplasia (BPH). The aim of the present study is to evaluate the effect of 2-hydroxy-4-methoxy benzoic acid (HMBA), a potential antioxidant on testosterone induced BPH in rats. Male Wistar rats were divided into five groups (n=6), Group I—received saline, Group II—received testosterone (3 mg/kg/s.c.), Group III—received testosterone+finasteride (5 mg/kg/oral), Group IV and V received testosterone+HMBA (200 and 400 μg/kg/i.p.), respectively, for 21 days. Animals were weighed before and after the study period. On 22nd day, animals were humanly killed by cervical dislocation. Prostates were excised and weighed, and used for biochemical and histological studies. As a result, testosterone treated rats showed increased prostate weight; prostatic index accompanied with depleted antioxidant enzymes levels, elevated lipid peroxides and total nitrite and associated histology disruption. HMBA treatment at 200 μg/kg/i.p. and 400 μg/kg/i.p. significantly restored (P<0.05) antioxidant enzyme levels, lipid peroxide and total nitrite when compared to disease control animals. It also ameliorated the testosterone induced histological changes. The present study suggests the protective role of HMBA on testosterone induced BPH by virtue of its antioxidant potential.     

NS309 decreases rat detrusor smooth muscle membrane potential and phasic contractions by activating SK3 channels

Background and Purpose

Overactive bladder (OAB) is often associated with abnormally increased detrusor smooth muscle (DSM) contractions. We used NS309, a selective and potent opener of the small or intermediate conductance Ca²⁺-activated K⁺ (SK or IK, respectively) channels, to evaluate how SK/IK channel activation modulates DSM function.

Experimental Approach

We employed single-cell RT-PCR, immunocytochemistry, whole cell patch-clamp in freshly isolated rat DSM cells and isometric tension recordings of isolated DSM strips to explore how the pharmacological activation of SK/IK channels with NS309 modulates DSM function.

Key Results

We detected SK3 but not SK1, SK2 or IK channels expression at both mRNA and protein levels by RT-PCR and immunocytochemistry in DSM single cells. NS309 (10 μM) significantly increased the whole cell SK currents and hyperpolarized DSM cell resting membrane potential. The NS309 hyperpolarizing effect was blocked by apamin, a selective SK channel inhibitor. NS309 inhibited the spontaneous phasic contraction amplitude, force, frequency, duration and tone of isolated DSM strips in a concentration-dependent manner. The inhibitory effect of NS309 on spontaneous phasic contractions was blocked by apamin but not by TRAM-34, indicating no functional role of the IK channels in rat DSM. NS309 also significantly inhibited the pharmacologically and electrical field stimulation-induced DSM contractions.

Conclusions and Implications

Our data reveal that SK3 channel is the main SK/IK subtype in rat DSM. Pharmacological activation of SK3 channels with NS309 decreases rat DSM cell excitability and contractility, suggesting that SK3 channels might be potential therapeutic targets to control OAB associated with detrusor overactivity.     

Synthesis, characterization, and antimicrobial activity of some new 2-diazo-benzimidazole derivatives and their Ni(II), Cu(II), and Ag(I) complexes

2-Aminobenzimidazole was diazotized and made to react with active methylene compounds viz: ethylcyanoacetate and malanonitrile. The ligands [IIIa and IIIb] were isolated, characterized, and then condensed with Ni(II) chloride, Cu(II) chloride, and Ag(I) nitrate. The ligands and complexes were characterized by elemental analysis, IR, ¹H NMR, ESR, UV–Visible spectral techniques, and along with thermal studies. The antimicrobial activity of the ligands [IIIa (C₁₂H₁₁N₅O₂) and IIIb (C₁₀H₆N₆)] and their metal complexes [IVa–IVf] against bacterial strains and fungal strains were investigated. The antimicrobial activity of the above metals and the ligands were discussed.     

A new synthetic TLR4 agonist, GLA, allows dendritic cells targeted with antigen to elicit Th1 T-cell immunity in vivo

Protein‐based vaccines offer safety and cost advantages but require adjuvants to induce immunity. Here we examined the adjuvant capacity of glucopyranosyl lipid A (GLA), a new synthetic non‐toxic analogue of lipopolysaccharide. In mice, in comparison with non‐formulated LPS and monophosphoryl lipid A, formulated GLA induced higher antibody titers and generated Type 1 T‐cell responses to HIV gag‐p24 protein in spleen and lymph nodes, which was dependent on TLR4 expression. Immunization was greatly improved by targeting HIV gag p24 to DCs with an antibody to DEC‐205, a DC receptor for antigen uptake and processing. Subcutaneous immunization induced antigen‐specific T‐cell responses in the intestinal lamina propria. Immunity did not develop in mice transiently depleted of DCs. To understand how GLA works, we studied DCs directly from vaccinated mice. Within 4 h, GLA caused DCs to upregulate CD86 and CD40 and produce cytokines including IL‐12p70 in vivo. Importantly, DCs removed from mice 4 h after vaccination became immunogenic, capable of inducing T‐cell immunity upon injection into naïve mice. These data indicate that a synthetic and clinically feasible TLR4 agonist rapidly stimulates full maturation of DCs in vivo, allowing for adaptive immunity to develop many weeks to months later.     

Utility of neutrophil CD64 and serum TREM-1 in distinguishing bacterial infection from disease flare in SLE and ANCA-associated vasculitis

Clinical Rheumatology - Bacterial and opportunistic infections are a major cause of morbidity and mortality in patients with systemic lupus erythematosus (SLE) and antineutrophil cytoplasmic...