Protective effect of MOTILIPERM in varicocele-induced oxidative injury in rat testis by activating phosphorylated inositol requiring kinase 1α (p-IRE1α) and phosphorylated c-Jun N-terminal kinase (p-JNK) pathways

Context: MOTILIPERM was prepared as a mixture of extracts of three medicinal herbs [roots of Morinda officinalis How (Rubiaceae), outer scales of Allium cepa L. (Liliaceae) and seeds of Cuscuta chinensis Lamark (Convolvulaceae)].

Objective: To investigate the role of reactive oxygen species (ROS)-based endoplasmic reticulum (ER) stress in a rat model of varicocele and the therapeutic efficacy of MOTILIPERM in this model.

Materials and methods: Sixty male rats were divided into five experimental groups: a normal control group (CTR?+?vehicle), a control group administered MOTILIPERM 200?mg/kg (CTR?+?M 200), a varicocele-induced control group (VC?+?vehicle) and two varicocele-induced groups administered MOTILIPERM 100 (VC?+?M 100) or 200 (VC?+?M 200) mg/kg for 4 weeks. Testis weights were recorded and serums were assayed for hormone concentrations. Tissues were subjected to semen analysis, histopathology, analyses of ER response protein expression levels and oxidative stress were assessed by measuring ROS, reactive nitrogen species (RNS), malondialdehyde (MDA) level and ratios of total glutathione (GSH)/oxidized GSH (GSSG).

Results: MOTILIPERM treatment of varicocele-induced groups significantly increased left testis weight, testosterone level, sperm motility, count and spermatogenic cell density. ER-response protein expression levels were dose-dependently decreased in VC?+?M 200 group compared with VC?+?vehicle group. MOTILIPERM treatment also decreased MDA and ROS/RNS level but increased GSH/GSSG ratio.

Discussion and conclusions: This study suggests that ROS-related ER stress may play a major role in varicocele-induced infertility and MOTILIPERM, a novel compound targeting ROS-based ER stress, may be therapeutically useful in treatment of varicocele, or as a supplement for the treatment of infertility.     

Comparison of the effect of asphyxia, hypoxia, and acidosis on intestinal blood flow and O2 uptake in newborn piglets

The aim of our study was to compare the effects of asphyxia and the two components of asphyxia, i.e. hypoxia and acidosis, on intestinal blood flow and oxygen consumption in anesthetized newborn piglets less than 3 days old. The first series of experiments, consisting of four groups of piglets, showed that blood flow to the proximal and distal small intestine and colon (as determined by the microsphere technique) significantly decreased after piglets were subjected to a sustained hypoxic hypoxemia (PaO2 50% of control) or asphyxia (acidosis plus hypoxia) for 90 min. A sustained acidosis (arterial pH = 7.0-7.15 for 90 min), however, decreased blood flow only to the proximal small intestine, and sham operation did not significantly alter any intestinal blood flow. All animals subjected to asphyxia and two of five of the animals subjected to hypoxia alone in this series, produced gross and microscopic intestinal lesions similar to those seen in human newborn with necrotizing enterocolitis. Acidosis alone, however, did not produce any pathologic lesions. The second series of experiments showed that the 90-min hypoxic hypoxemia decreased blood flow to both the mucosa and muscularis layers of the small intestine. The third series of experiments, consisting of four groups of piglets, determined the effects of 60-min acidosis, hypoxic hypoxemia, asphyxia, or sham operation on venous outflow and oxygen consumption of the isolated in situ terminal ileum. Acidosis or sham operation altered neither ileal blood flow nor oxygen consumption. Hypoxia or asphyxia, however, decreased ileal oxygen consumption without significantly decreasing blood flow.(ABSTRACT TRUNCATED AT 250 WORDS)     

Melanin potentiates gentamicin-induced inhibition of collagen biosynthesis in human skin fibroblasts

One of the recognized side effects of gentamicin is ototoxicity. The mechanism underlying the organ specificity of this side effect of gentamicin has not been fully established. In view of the fact that a number of pharmacologic agents are known to form complexes with melanin and melanin is an abundant constituent of the inner ear tissues, we determined whether gentamicin interacts with melanin and how this process affects the biosynthesis of collagen in cultured human skin fibroblasts. Our results indicate that gentamicin forms complexes with melanin. The amount of gentamicin bound to melanin increases with increasing of initial drug concentration. The Scatchard plot analysis of drug binding to melanin showed that at least two classes of independent binding sites are implicated in gentamicin-melanin complex formation: one class with an association constant K(1) approximately 4 x 10(3) M(-1), and the second class with an association constant K(2) approximately 3 x 10(2) M(-1). The number of total binding sites (n(1)+n(2)) was calculated as about 1.36 micromol gentamicin per 1 mg melanin. We have suggested that prolidase, an enzyme involved in collagen metabolism, may be one of the targets for gentamicin-induced inhibition of collagen biosynthesis. We found that gentamicin-induced inhibition of prolidase activity (IC(50) approximately 100 microM) and collagen biosynthesis (IC(50) approximately 100 microM). At this concentration of gentamicin, DNA biosynthesis in human skin fibroblasts was inhibited only by about 30%. Melanin at 100 microg/ml produced about 25% inhibition of DNA synthesis and about 30% inhibition of prolidase activity, but it had no effect on collagen biosynthesis in cultured fibroblasts. However, the addition of melanin (100 microg/ml) to gentamicin-treated cells (100 microM) augmented the inhibitory action of gentamicin on collagen and DNA biosynthesis and partially reversed its inhibitory effect on prolidase activity. A melanin-induced augmentation of the inhibitory effects of gentamicin on collagen and DNA biosynthesis may explain the mechanism for the organ specificity of gentamicin-induced hearing loss in patients administered this drug.     

Retinopathy of prematurity and risk factors: a prospective cohort study

Background  

Increased survival of extremely low birth infants due to advances in antenatal and neonatal care has resulted in a population of infants at high risk of developing retinopathy of prematurity (ROP). Therapeutic interventions include the use of antenatal and postnatal steroids however, their effects on the severity of ROP is in dispute. In addition, it has not been investigated whether severe ROP is due to therapeutic interventions or due to the severity of illness. The aim of the present study was to assess the association between the incidence of severe retinopathy of prematurity (greater than stage 2 – International classification of ROP) and mechanical ventilation, oxygen therapy, gestational age, antenatal and postnatal steroids in extremely low birth weight infants.     

Video and CD-ROM as a training tool for performing neurologic examinations of 1-year-old children in a multicenter epidemiologic study

In lieu of traditional training of examiners to identify cerebral palsy on a neurologic examination at age 1 year, we proposed an alternative approach using a multimedia training video and CD-ROM we developed after a two-step validation process. We hypothesized that use of CD-ROM interactive training will lead to reliable and valid performance of the neurologic examination by both pediatric neurologists and nonpediatric neurologists. All examiners were asked to take one of six interobserver variability tests found on the CD-ROM on two occasions. In the first interobserver variability evaluation, 89% (531 of 594) of the responses agreed with the gold standard responses. Following annotated feedback to the examiners about the two items that had a 60% correct rate, the correct response rate rose to 93% (114 of 123). In the second interobserver variability evaluation, 88% (493 of 560) of the responses agreed with the gold standard responses. Following annotated feedback to the examiners about the four items that had a 70% correct rate, the correct response rate rose to 96% (104 of 108). Interactive CD-ROM examination training is an efficient and cost-effective means of training both neurologists and non-neurologists to perform structured neurologic examinations in 1-year-old children. It provides an effective means to evaluate interobserver variability, offers a route for feedback, and creates an opportunity to reevaluate variability, both immediately and at periodic intervals.     

Specific compliance and gas exchange during high-frequency oscillatory ventilation

OBJECTIVES: To evaluate the use of specific compliance (static compliance/functional residual capacity) to adjust mean airway pressure, resulting in optimal gas exchange during high-frequency oscillatory ventilation in a surfactant-deficient newborn piglet. DESIGN: Prospective controlled animal study. SETTING: Laboratory. SUBJECTS: Eight newborn piglets at 5 days of age. BACKGROUND: High-frequency oscillatory ventilation enables the use of relatively high mean airway pressures without the lung damage associated with conventional positive pressure ventilation. Mean airway pressures can be increased, resulting in static lung expansion that approaches total lung capacity with its negative impact on venous return. Therefore, knowledge of lung volume is important for safe patient management. A simple, noninvasive technique to enable the clinician to determine the optimal mean airway pressure likely would improve patient management. INTERVENTIONS: The lungs were lavaged after placement of central catheters and tracheostomy to lower respiratory system compliance and worsen ventilation perfusion matching. The animals were ventilated with high-frequency oscillatory ventilation at the same mean airway pressure as before lung lavage. Mean airway pressures then were increased in a step-wise fashion up to 30 cm H2O or until clinical deterioration occurred. All other ventilator variables, Fio2, frequency, and pressure amplitude were constant throughout the experiment. MEASUREMENTS AND MAIN RESULTS: Before lavage and at each level of mean airway pressure after lung lavage, respiratory system compliance and functional residual capacity were measured. Additionally, central arterial pressure, central venous pressure, heart rate, arterial blood gas, and pulse oximetric saturation were recorded. Lung lavage significantly lowered respiratory system compliance (static as well as specific compliance) and worsened ventilation perfusion matching as evidenced by an increase in Paco2 and a decreased arterial to alveolar oxygen ratio. With increasing mean airway pressures, static/specific compliance improved and then peaked before declining, functional residual capacity increased, and blood gas improved until reaching the flat portion of the pressure-volume relationship of the lung. Optimal gas exchange as reflected by the highest arterial to alveolar oxygen ratio and lowest Paco2 at constant ventilation was found at a mean airway pressure that maintained the functional residual capacity and static respiratory system compliance at the same level as the preinjury levels ("normalized" functional residual capacity and respiratory system compliance). CONCLUSIONS: These results suggest that specific compliance measurement that incorporates static respiratory system compliance and functional residual capacity during high-frequency oscillatory ventilation can be used to adjust mean airway pressure and achieve "normalized" functional residual capacity, static compliance, and gas exchange. These measurements may provide a simple method to optimize lung volume in a surfactant-deficient patient during high-frequency oscillatory ventilation.     

Multiple cranial nerve palsy in an HIV-positive patient

We report the case of a 32 -year- old HIV-positive Indian male who presented with sixth nerve (bilateral), ninth, tenth and twelfth nerve palsies; cerebellar and posterior column involvement. CT scan showed gyriform enhancement in the right occipital lobe and nodular leptomeningeal enhancement in the left frontal lobe. Cytomegalovirus serology was positive and the patient was treated as presumed CMV. HIV can present with multiple cranial neuropathy and varied neurological involvement.     

Resolution of chicken pox neuroretinitis with oral acyclovir: A case report

It is usual to consider chicken pox as a benign infectious disease with a few anterior segment ocular complications like conjunctivitis, keratitis, episcleritis, scleritis, iridocyclitis, and glaucoma. The retinal manifestations are necrotising retinitis, vitritis, neuroretinitis, and retinal detachments. We report a case of neuroretinitis following chicken pox in a 23-year-old male. The complication was resolved by treatment with oral acyclovir in combination with systemic steroids. This report highlights the necessity for fundus examination in cases of chickenpox exhibiting visual symptoms.