Oxidative,inflammatory and immunologic status in children with undescended testes

Background: In order to better understand the pathogenesis of risk of future sub‐/infertility in children with undescended testes (UDT), we designed this prospective study to examine the oxidative stress, inflammatory response and autoimmunity in children with UDT. We examined the concentrations of malondialdehyde (MDA), interleukin‐6 (IL‐6) and antisperm antibodies (ASA) in children with UDT and healthy controls. Methods: The UDT group consisted of 88 boys (aged 1–14 years, unilateral in 67 and bilateral in 21 cases), and 44 boys with normal descended testes served as a control group. Clinical evaluation revealed no testicular or other system abnormalities. MDA was used as lipid peroxidation index. IL‐6 levels were measured using a commercial enzyme‐linked immunosorbent assay kit. ASA was determined with an anti‐human spermatozoa immunoglobulin G test. Results: Mean age values ± SD were 4.6 ± 3.2 in the UDT group and 4.7 ± 3.4 in the control group (P= 0.872). MDA and IL‐6 results for the UDT and control groups were significantly different (P= 0.003 and P= 0.019, respectively), but those for ASA were not (P= 0.473). The mean MDA and IL‐6 values were significantly higher in bilateral cases than the respective values in the unilateral cases (MDA: 4.03 ± 3.68 vs 3.49 ± 5.22, P= 0.015; IL‐6: 7.70 ± 6.86 vs 3.48 ± 6.50, P= 0.001) (P= 0.015). Conclusion: The results indicate that children with UDT are exposed to high levels of oxidative stress and inflammatory reaction. This could negatively affect the future fertility in these children.     

Optic neuropathy and chiasmopathy as presenting manifestations of systemic lupus erythematosus

A patient presented with subacute onset of bilateral visual loss associated with malaise, arthralgias, and itching. Her visual acuity was at the level of light perception in both eyes with bilaterally dilated, poorly reactive pupils and papilledema. The magnetic resonance imaging (MRI) revealed enlargement and enhancement with gadolinium of the optic nerves and the chiasm. She was diagnosed with systemic lupus erythematosus (SLE) based on the clinical, radiological, and laboratory findings.     

Diagnostic value of thyroglobulin measurement in fine-needle aspiration biopsy for detecting metastatic lymph nodes in patients with papillary thyroid carcinoma

Purpose  

We aimed to compare the diagnostic value of fine-needle aspiration cytology (FNAC) and fine-needle aspiration thyroglobulin measurements (FNA-Tg) for detecting cervical lymph node metastases from differentiated thyroid carcinomas.     

Cardiovascular diseases in obstructive sleep apnea

Obstructive sleep apnea (OSA) affects approximately 5% of women and 15% of men in the middle-aged adults, and associated with adverse health outcomes. Cardiovascular disturbances are the most serious complications of OSA. These complications include heart failure, left/right ventricular dysfunction, acute myocardial infarction, arrhythmias, stroke, systemic and pulmonary hypertension. All these cardiovascular complications increase morbidity and mortality of OSA. Several epidemiologic studies have demonstrated that sleep related breathing disorders are an independent risk factor for hypertension, probably resulting from a combination of intermittent hypoxia and hypercapnia, arousals, increased sympathetic activity, and altered baroreflex control during sleep. Arterial hypertension, obesity, diabetes mellitus and coronary artery disease (CAD) which are independent predictors of left ventricular dysfunction, often have co-existence with OSA. Especially severe OSA patients having diastolic dysfunction might have an increased risk of heart failure, since diastolic dysfunction might be combined with systolic dysfunction. Early recognition and appropriate therapy of ventricular dysfunction is advisable to prevent further progression to heart failure and death. Patients with acute myocardial infarction, especially if they had apneas and hypoxemia without evident heart failure should be evaluated for sleep disorders. So, patients with CAD should be evaluated for OSA and vice versa. Early recognition and treatment of OSA may improve cardiovascular functions. Continuous positive airway pressure (CPAP) applied by nasal mask, is still the gold standard method for treatment of the disease and prevention of complications.     

Caspase 9 is decreased in psoriatic epidermis

Psoriasis is a proliferative and inflammatory disease of the skin. Caspase 9 is responsible for initiating the caspase activation cascade during apoptosis. Apoptosis is a physiological mechanism of homeostasis and development, and caspases are the executioners of apoptosis. This study reports the immunohistochemical localisation of caspase 9 in psoriatic skin and compares it with that seen in normal, healthy control skin. Skin biopsy specimens of lesions were obtained from 15 patients with plaque type psoriasis vulgaris. The specimens were labelled immunohistochemically for binding of an anti-caspase 9 primary antibody. Biopsies of healthy skin from 10 age-matched and sex-matched healthy control individuals were also analysed. The caspase 9 positive cell fraction was calculated for both epidermal and dermal cells in psoriatic lesions and healthy control skin. Counts of caspase 9 positive cells from the epidermis of psoriatic skin lesions were significantly lower than those seen in healthy skin (p<0.05). The caspase 9 immunolabelled perivascular cell counts in the dermis were not statistically significantly different in psoriatic lesions versus normal skin (p>0.05). Psoriatic epidermis contains little of the apoptotic marker, caspase 9. The results of this study are indicative of decreased apoptosis in psoriatic epidermis, and no change in the perivascular area in psoriatic lesions. These findings support the idea that decreased apoptosis is seen in psoriatic epidermal cells. Greater understanding of the nature of the disease may open new avenues for further therapeutic modalities.     

Urocortin 2 modulates glucose utilization and insulin sensitivity in skeletal muscle

Skeletal muscle is the principal tissue responsible for insulin-stimulated glucose disposal and is a major site of peripheral insulin resistance. Urocortin 2 (Ucn 2), a member of the corticotropin-releasing factor (CRF) family, and its cognate type 2 CRF receptor (CRFR2) are highly expressed in skeletal muscle. To determine the physiological role of Ucn 2, we generated mice that are deficient in this peptide. Using glucose-tolerance tests (GTTs), insulin-tolerance tests (ITTs), and hyperinsulinemic euglycemic glucose clamp studies, we demonstrated that mice lacking Ucn 2 exhibited increased insulin sensitivity and were protected against fat-induced insulin resistance. Administration of synthetic Ucn 2 to mutant mice before the GTTs and ITTs restored blood glucose to WT levels. Administration of a CRFR2 selective antagonist to WT mice resulted in a GTT profile that mirrored that of Ucn 2-null mice. Body composition measurements of Ucn 2-null mice on a high-fat diet demonstrated decreases in fat and increases in lean tissue compared with WT mice. We propose that null mutant mice display increased glucose uptake in skeletal muscle through the removal of Ucn 2-mediated inhibition of insulin signaling. In keeping with these data, Ucn 2 inhibited insulin-induced Akt and ERK1/2 phosphorylation in cultured skeletal muscle cells and C2C12 myotubes. These data are consistent with the hypothesis that Ucn 2 functions as a local negative regulator of glucose uptake in skeletal muscle and encourage exploration of the possibility that suppression of the Ucn 2/CRFR2 pathway may provide benefits in insulin-resistant states such as type 2 diabetes.     

Inflammatory mediators accelerate metabolism of benzo[a]pyrene in rat alveolar type II cells: The role of enhanced cytochrome P450 1B1 expression

Long-term deregulated inflammation represents one of the key factors contributing to lung cancer etiology. Previously, we have observed that tumor necrosis factor-α (TNF-α), a major pro-inflammatory cytokine, enhances genotoxicity of benzo[a]pyrene (B[a]P), a highly carcinogenic polycyclic aromatic hydrocarbon, in rat lung epithelial RLE-6TN cells, a model of alveolar type II cells. Therefore, we analyzed B[a]P metabolism in RLE-6TN cells under inflammatory conditions, simulated using either recombinant TNF-α, or a mixture of inflammatory mediators derived from activated alveolar macrophage cell line. Inflammatory conditions significantly accelerated BaP metabolism, as evidenced by decreased levels of both parent B[a]P and its metabolites. TNF-α altered production of the metabolites associated with dihydrodiol-epoxide and radical cation pathways of B[a]P metabolism, especially B[a]P-dihydrodiols, and B[a]P-diones. We then evaluated the role of cytochrome P450 1B1 (CYP1B1), which is strongly up-regulated in cells treated with B[a]P under inflammatory conditions, in the observed effects. The siRNA-mediated CYP1B1 knock-down increased levels of B[a]P and reduced formation of stable DNA adducts, thus confirming the essential role of CYP1B1 in B[a]P metabolism under inflammatory conditions. TNF-α also reduced expression of aldo-keto reductase 1C14, which may compete with CYP1B1 for B[a]P-7,8-dihydrodiol and divert it from the formation of ultimate B[a]P dihydrodiol epoxide. Together, the present data suggests that the CYP1B1-catalyzed metabolism of polycyclic aromatic hydrocarbons might contribute to their enhanced bioactivation and genotoxic effects under inflammatory conditions.     

Vasoactive Intestinal Peptide Enhances Striatal Plasticity and Prevents Dopaminergic Cell Loss in Parkinsonian Rats

Destruction of the nigrostriatal dopaminergic pathway by the administration of 6-OHDA generates an animal model of Parkinson's disease. The main characteristic of this progressive neurological disorder is the loss of the dopaminergic neurons located in the substantia nigra pars compacta (SNc). Dopaminergic inputs from the SNc innervate the medium spiny neurons of the striatum and modulate the spontaneous activity of the primary output nuclei of the basal ganglia, globus pallidus interna, and substantia nigra pars reticulata. In our previous studies, we showed that systematically administered vasoactive intestinal peptide (VIP) is effective at reversing motor deficits, decreasing neuronal cell death, and repairing the myelin sheet in parkinsonian rats. In the current study, the effects of VIP on the dendritic morphology of the striatal neurons and the number of dopaminergic neurons in the SNc were examined in 6-OHDA-lesioned rats using Golgi-Cox staining and design-based stereological methods, respectively. Adult Sprague-Dawley rats were separated into sham-operated, bilaterally 6-OHDA lesioned and lesioned + i.p. VIP-injected (25?ng/kg) groups. VIP was first injected 1?h after the intrastriatal 6-OHDA microinjection (every 2?days for 15?days). The 6-OHDA significantly decreased the total number of dopaminergic neurons, branching, and spine density of the medium spiny neurons in the striatum. VIP significantly increased the number of neurons immunostained with tyrosine hydroxylase and the density of spines without altering the branching and the total length of dendrites. In conclusion, VIP might display synaptogenetic activity by enhancing the spine density in the striatum of the parkinsonian rats.