NPHS2 (podicin) mutations in Turkish children with idiopathic nephrotic syndrome

The podocin (NPHS2) gene encodes podocin protein, which has an important role in glomerular ultrafiltration and controlling slit membrane permeability. The detection of an NPHS2 mutation affects the treatment plan for children with nephritic syndrome (NS). The frequency and spectrum of podocin mutations in the Turkish population have remained largely unknown. The aim of this study was to screen for podocin mutations in Turkish patients with steroid-resistant NS (SRNS) and to compare it with other published series. There were 295 children with SRNS, originating from Turkey, included in this study. Forty-one patients (13.8%) had familial NS and 254 patients (86.2%) had sporadic NS. Mutation analysis was performed in all eight exons of the NPHS2 gene with the direct DNA sequencing method. There were 53 different pathogenetic NPHS2 mutations detected, including 37 novel mutations. The mutation detection rate was 24.7% for all patients, 29.2% for familial, and 24% for sporadic SRNS. The most common mutated exon was exon 5 (52 allele). The presence of mutations in exon 4 was found to increase the risk of end-stage renal disease (ESRD). Among patients with mutations, the rates of renal failure and/or ESRD (26%) were significantly higher than in those without mutations (12.6%). The mean time of progression to renal failure and ESRD in patients with mutations (1.8 ± 2.5 years) was significantly shorter than in patients without mutations (3.7 ± 4.0 years). Additionally, in patients with heterozygote mutations, fewer cases (13.6%) progressed to renal failure and/or ESRD than in with patients who had homozygote/compound heterozygote mutations (31.3%). In conclusion, podocin mutations are responsible for some of both familial and sporadic SRNS cases in Turkey. The mutations in this gene should be searched for in every child after presentation with the first episode of NS.     

Efficacies of caspofungin and a combination of caspofungin and meropenem in the treatment of murine disseminated candidiasis

Disseminated candidiasis is relatively common in immunocompromised patients. The treatment protocol of these patients usually includes broad-spectrum antibiotics and also emprical antifungals initiated due to unresponsiveness to antibiotics. In this study the efficacies of caspofungin and meropenem - separately and together - in mice with disseminated candidiasis were studied. Immunocompetent mice were infected intravenously with 2x10(6) CFU of Candida albicans. At 24 h postinfection, intraperitoneal therapy was initiated and was continued for 7 days. Therapy groups included those given caspofungin (0.5, 1.25, 5 mg/kg/day), meropenem (20 mg/kg/day), and a combination of the two drugs. The outcome of therapy was evaluated by kidney tissue burden studies and histologic examination. In vitro, drug susceptibilities were tested by checkerboard analysis. Kidney CFU counts showed that mice that had received both drugs had lower residual burdens. Caspofungin was effective at doses of 0.5, 1.25, 5 mg/kg compared to infected untreated controls. In vitro, MICs of caspofungin and meropenem were <0.075 micro g/ml and >64 micro g/ml, respectively. Synergism was observed with the combination. Histopathology showed that the degree of inflammation was 25% less and tubular necrosis was more restricted in combined therapy than monotherapy. The results indicate that concurrent caspofungin and meropenem therapy may be beneficial.     

Beneficial Pharmacological Effects of Levosimendan on Antioxidant Status of Acute Inflammation Induced in Paw of Rat: Involvement in Inflammatory Mediators

Levosimendan (LEVO) is a new calcium sensitizer with positive inotropic and vasodilating properties that represents a new pharmacological class of inotropic drugs that stimulate elevated cardiac output. The purpose of this study was to examine anti‐inflammatory effect and antioxidant activity of LEVO in a carrageenan (CAR)‐induced inflammatory paw oedema rat model. The CAR‐induced rat groups received LEVO 1, 2 and 3 mg/kg by intraperitonally and indomethacin (IND) 25 mg/kg by oral gavage. LEVO inhibited CAR‐induced paw oedema and suppressed the production of TNF‐α, IL‐1 and IL‐6 at doses of 2 and 3 mg/kg. In contrast to CAR‐injected paws, 2 and 3 mg/kg doses of LEVO and IND increased superoxide dismutase (SOD) activity and also both doses of LEVO, and IND decreased the 8‐isoprostaglandin F2α (8‐ISO) level. A 2 mg/kg dose of LEVO produced 39%, 46%, 61% and 64.7% anti‐inflammatory effects (p < 0.0001) for the 1st, 2nd, 3rd and 4th hours, respectively. Other results of our current study have shown that SOD and glutathione for CAR‐injected groups were lower, and 8‐ISO level was higher than those for the healthy rat group. LEVO may be provided as a pharmacological agent in the prevention or treatment of diseases in which acute or chronic inflammation occurs based on a pathogenic factor.     

Medium-latency reflex response elicited from the flexor carpi radialis by radial nerve stimulation

The H reflex obtained from the flexor carpi radialis muscle by median nerve stimulation is a well-known monosynaptic reflex. However, the origin of the late responses is still contentious. Radial nerve stimulation was performed through the spiral groove, and EMG recording was obtained from the flexor carpi radialis (FCR) and extensor carpi radialis (ECR) muscles. An M response followed by an F response was achieved from the ECR by radial nerve stimulation; the antagonistic FCR muscle elicited a late response. A total of 25 cases were included in this study. In 22 of these cases, a response with a latency of 40.97 ± 5.35 ms was obtained from the FCR by radial nerve stimulation. When extension of the hand was restricted, the response disappeared in five of nine cases. Application of cold markedly suppressed the response and prolonged the latency of the FCR medium-latency reflex response (FCR-MLR). Oral tizanidine considerably suppressed the FCR-MLR response. Two out of eight cases did not exhibit any response. No response could be recorded from a patient with complete amputation of the right hand. The FCR-MLR is the reflex caused by stretching of the FCR muscle from radial nerve stimulation, and it is greatly influenced by group II afferents.     

Effect of Resveratrol on Treatment of Bleomycin-Induced Pulmonary Fibrosis in Rats

Resveratrol has a preventive potential on bleomycin-induced pulmonary fibrosis in prophylactic use; however, it was not studied in the treatment of the fibrosis. This study investigated the role of resveratrol on the treatment of bleomycin-induced pulmonary fibrosis. Intratracheal bleomycin (2.5?mg/kg) was given in fibrosis groups and saline in controls. First dose of resveratrol was given 14?days after bleomycin and continued until sacrifice. On 29th day, fibrosis in lung was estimated by Aschoft's criteria and hydroxyproline content. Bleomycine increased the fibrosis score (3.70?±?1.04) and hydroxyproline levels (4.99?±?0.90?mg/g tissue) as compared to control rats (1.02?±?0.61 and 1.88?±?0.59?mg/g), respectively. These were reduced to 3.16?±?1.58 (P?=?0.0001) and 3.08?±?0.73 (P?>?0.05), respectively, by resveratrol. Tissue malondialdehyde levels in the bleomycin-treated rats were higher (0.55?±?0.22?nmol/mg protein) than that of control rats (0.16?±?0.07; P?=?0.0001) and this was reduced to 0.16?±?0.06 by resveratrol (P?=?0.0001). Tissue total antioxidant capacity is reduced (0.027?±?0.01) by bleomycine administration when compared control rats (0.055?±?0.012?mmol Trolox Equiv/mg protein; P?=?0.0001) and increased to 0.041?±?0.008 (P?=?0.001) by resveratrol. We concluded that resveratrol has some promising potential on the treatment of bleomycin-induced pulmonary fibrosis in rats. However, different doses of the drug should be further studied.     

Detection of Resistivity for Antibiotics by Probabilistic Neural Networks

This paper presents the use of probabilistic neural networks (PNNs) for detection of resistivity for antibiotics (resistant and sensitive). The PNN is trained on the resistivity or sensitivity to the antibiotics of each record in the Salmonella database. Estimation of the whole parameter space for the PNN was performed by the maximum-likelihood (ML) estimation method. The expectation-maximization (EM) approach can help to achieve the ML estimation via iterative computation. Resistivity and sensitivity of the three antibiotics (ampicillin, chloramphenicol disks and trimethoprim–sulfamethoxazole) were classified with high accuracies by the PNN. The obtained results demonstrated the success of the PNN to help in detection of resistivity for antibiotics.     

Respiratory function and immunological status in workers employed in a latex glove manufacturing plant

A study was performed in 17 female workers employed in a latex glove manufacturing plant. The mean age of these workers was 42 years and the mean duration of their employment was 19 years. The employees were primarily nonsmokers or light smokers. The presence of chronic respiratory symptoms and acute work-related symptoms was recorded for these workers. Ventilatory capacity was measured during the morning work shift by recording maximum expiratory flow-volume curves from which forced vital capacity (FVC), 1-second forced expiratory volume (FEV₁) and maximum expiratory flow at 50%, and the last 25% of the vital capacity (FEF₅₀, FEF₇₅) were measured. A control group of 17 nonexposed women workers was also studied. The prevalence of chronic respiratory symptoms was greater among latex workers than among control confectionry packer workers, varying from 5.9% (vs. 0% in controls) for occupational asthma to 58.8% (vs. 0% in controls) for dyspnea grades 3 or 4. There was also a high prevalence of acute work-related symptoms in this industry, in particular, eye irritation (76.5%), dryness of the nose (70.6%), throat burning (70.6%), dryness of the throat (64.7%), and cough (58.8%). Among exposed workers, measured ventilatory capacity data were significantly lower than among controls, particularly FEF₇₅ (75.1% ± 10.5%). One of the 17 studied workers (5.9%) had a positive skin reaction to latex and had symptoms compatible with occupational asthma. Our data suggest that in addition to occupational asthma, the manufacture of latex gloves is associated with frequent, nonspecific respiratory findings. Am. J. Ind. Med. 33:175–181, 1998. © 1998 Wiley-Liss, Inc.