Frequency of Heterotic Hybrids in Relation to Parental Genetic Divergence and General Combining Ability in Dolichos Bean

Though F₁ hybrids are not the immediate cultivar option, development of heterotic F₁ hybrids is relevant from view point of deriving pure lines, the only cultivar choice in dolichos bean, a predominantly self-pollinated grain legume crop species. Heterotic F₁ generates a high frequency of productive derivatives in F₃ and later generations as compared to non-heterotic F₁. The criteria such as combining ability and genetic diversity between parents are being commonly used to develop heterotic hybrids. In this context, an investigation was carried out at University of Agricultural Sciences, Bengaluru, India, to test the predictability of frequency of heterotic hybrids based on parental gca effects and genetic diversity in dolichos bean. The 48 F₁ hybrids generated by crossing 12 lines and 4 testers were evaluated along with their parents for 6 quantitative characters. The overall gca status (high and low) of each parent and overall sca and heterotic status (high and low) of each hybrid for 6 characters were determined. Based on overall gca status and genetic divergence of parents, the hybrids were grouped into different classes. The hybrids involving parents contrasting for overall gca status and/or those involving parents with intermediate genetic divergence were more frequently heterotic than those involving comparable gca status with extreme genetic divergence. Thus, there exists a limit to parental divergence for the occurrence of heterosis. It is hence, desirable to involve parents with intermediate genetic divergence and contrasting gca effects to recover higher frequencies of heterotic hybrids for economic traits in dolichos bean.     

Interaction between positive allosteric modulators and trapping blockers of the NMDA receptor channel

Background and Purpose

Memantine and ketamine are clinically used, open-channel blockers of NMDA receptors exhibiting remarkable pharmacodynamic similarities despite strikingly different clinical profiles. Although NMDA channel gating constitutes an important difference between memantine and ketamine, it is unclear how positive allosteric modulators (PAMs) might affect the pharmacodynamics of these NMDA blockers.

Experimental Approach

We used two different PAMs: SGE-201, an analogue of an endogenous oxysterol, 24S-hydroxycholesterol, along with pregnenolone sulphate (PS), to test on memantine and ketamine responses in single cells (oocytes and cultured neurons) and networks (hippocampal slices), using standard electrophysiological techniques.

Key Results

SGE-201 and PS had no effect on steady-state block or voltage dependence of a channel blocker. However, both PAMs increased the actions of memantine and ketamine on phasic excitatory post-synaptic currents, but neither revealed underlying pharmacodynamic differences. SGE-201 accelerated the re-equilibration of blockers during voltage jumps. SGE-201 also unmasked differences among the blockers in neuronal networks – measured either by suppression of activity in multi-electrode arrays or by neuroprotection against a mild excitotoxic insult. Either potentiating NMDA receptors while maintaining the basal activity level or increasing activity/depolarization without potentiating NMDA receptor function is sufficient to expose pharmacodynamic blocker differences in suppressing network function and in neuroprotection.

Conclusions and Implications

Positive modulation revealed no pharmacodynamic differences between NMDA receptor blockers at a constant voltage, but did expose differences during spontaneous network activity. Endogenous modulator tone of NMDA receptors in different brain regions may underlie differences in the effects of NMDA receptor blockers on behaviour.     

Neurological manifestations of hepatitis E virus infection: An overview

Hepatitis E virus (HEV) is an important cause of repeated waterborne outbreaks of acute hepatitis. Recently, several extrahepatic manifestations (EHMs) have been described in patients with HEV infection. Of these, neurological disorders are the most common EHM associated with HEV. The involvement of both the peripheral nervous system and central nervous system can occur together or in isolation. Patients can present with normal liver function tests, which can often be misleading for physicians. There is a paucity of data on HEV-related neurological manifestations; and these data are mostly described as case reports and case series. In this review, we analyzed data of 163 reported cases of HEV-related neurological disorders. The mechanisms of pathogenesis, clinico-demographic profile, and outcomes of the HEV-related neurological disorders are described in this article. Nerve root and plexus disorder were found to be the most commonly reported disease, followed by meningoencephalitis.     

Assessment of mitral valvar stenosis by echocardiography: utility of various methods before and after mitral valvotomy.

Cross-sectional and Doppler echocardiography are currently the most important non-invasive tests for the evaluation of mitral stenosis. Recent experience has, however, shown that parameters that are reliable before mitral valvotomy may not be valid after the procedure. We have studied the validity of estimation of the area of the mitral valve by echo-planimetry, by Doppler pressure half time and the transmitral end-diastolic pressure gradient calculated by continuous wave Doppler in 100 patients (aged 10-30 years) before and after balloon mitral valvoplasty (n = 70) or surgical closed mitral valvotomy (n = 30). These patients underwent cardiac catheterisation and echocardiographic studies before, immediately after and 8-12 (9.3 +/- 2.2) weeks following balloon valvoplasty or closed valvotomy. The area as estimated echocardiographically correlated well with that obtained by the Gorlin formula before (r = 0.80), but not immediately after (r = 0.67) or on follow up after mitral valvotomy. There was good correlation between Doppler pressure half time and the area as estimated by the Gorlin formula before (r = 0.89) and on follow up after valvotomy (r = 0.82), but the correlation was not as good in the immediate period after valvotomy (r = 0.60). The end-diastolic pressure gradients obtained by Doppler examination and at cardiac catheterisation correlated well with each other before (r = 0.94), immediately after valvotomy (r = 0.92) and on follow up (r = 0.94). Hence, the reliability of estimation of the area of the mitral valve by echo-planimetry and by Doppler pressure half time varies according to the time at which the examination is performed following commissurotomy.(ABSTRACT TRUNCATED AT 250 WORDS)     

Lower esophageal sphincter pressures in patients of bronchial asthma and its correlation with spirometric parameters: a case-control study

Objectives: The cause–effect relationship between bronchial asthma and gastro-esophageal reflux (GER) is known, but studies have not been able to confirm the improvement of lung function with anti-acid therapy. Hypotensive lower esophageal sphincter (LES) may lead to both acid and non-acid reflux, resulting in asthma symptoms and decreased lung function. The objectives of our study were, firstly, to compare basal LES pressure between adult patients of asthma and normal controls and, secondly, to correlate the basal LES pressure with spirometric parameters in these patients. Methods: Thirty patients, aged between 18 and 65 years, diagnosed as cases of bronchial asthma and 27 healthy controls were included in the study. All the participants were subjected to esophageal manometry after overnight fasting and basal LES pressures were recorded. Then, spirometry was done 2?h after meal and pre- and post-bronchodilator FEV₁, FVC, PEFR were obtained for the asthma group. Results and conclusions: There is significant difference between basal LES pressure in patients of bronchial asthma and control population (8.70?±?2.67?mmHg versus 16.64?±?5.52, p?<?0.0001). 66.67% of the asthma patients have reduced LES pressures (<10?mmHg). The correlation coefficient between basal LES pressure and prebronchodilator FEV₁% predicted is 0.596 (p?<?0.0001, 95% CI 0.3002–0.7872). Obstructive airway impairment in adult patients of bronchial asthma is associated with hypotensive LES. GER, due to hypotensive LES may contribute to deterioration of spirometric parameters in asthma patients.     

Pancreatic B-cell function in relation to diabetic retinopathy in Asian Indian NIDDM patients

Summary Pancreatic B-cell function in relation to diabetic retinopathy was studied in 195 NIDDM patients with long-standing diabetes. Background diabetic retinopathy (BDR) was present in 95 (48.7%) and proliferative retinopathy (PDR) in 17 (8.7%) of the subjects. There was no significant difference between the BDR, PDR, and non-retinopathy groups with respect to age, age at diagnosis of diabetes and HbA₁ values. Mean duration of diabetes was higher in the PDR group (p<0.05). Serum C-peptide values showed no correlation with the presence of retinopathy or with the duration of diabetes. The C-peptide values were widely scattered in patients with BDR and PDR showing no association between pancreatic B-cell reserve and occurrence or severity of retinopathy in NIDDM patients. Thus, decreased pancreatic B-cell reserve does not appear to be a risk factor for diabetic retinopathy in NIDDM patients.     

Telomere shortening occurs in Asian Indian Type 2 diabetic patients.

AIM: Telomere shortening has been reported in several diseases including atherosclerosis and Type 1 diabetes. Asian Indians have an increased predilection for Type 2 diabetes and premature coronary artery disease. The aim of this study was to determine whether telomeric shortening occurs in Asian Indian Type 2 diabetic patients. METHODS: Using Southern-blot analysis we determined mean terminal restriction fragment (TRF) length, a measure of average telomere size, in leucocyte DNA. Type 2 diabetic patients without any diabetes-related complications (n = 40) and age- and sex-matched control non-diabetic subjects (n = 40) were selected from the Chennai Urban Rural Epidemiology Study (CURES). Plasma level of malondialdehyde (MDA), a marker of lipid peroxidation, was measured by TBARS (thiobarbituric acid reactive substances) using a fluorescence method. RESULTS: Mean (+/- SE) TRF lengths of the Type 2 diabetic patients (6.01 +/- 0.2 kb) were significantly shorter than those of the control subjects (9.11 +/- 0.6 kb) (P = 0.0001). Among the biochemical parameters, only levels of TBARS showed a negative correlation with shortened telomeres in the diabetic subjects (r = -0.36; P = 0.02). However, telomere lengths were negatively correlated with insulin resistance (HOMA-IR) (r = -0.4; P = 0.01) and age (r = -0.3; P = 0.058) and positively correlated with HDL levels (r = 0.4; P = 0.01) in the control subjects. Multiple linear regression (MLR) analysis revealed diabetes to be significantly (P < 0.0001) associated with shortening of TRF lengths. CONCLUSIONS: Telomere shortening occurs in Asian Indian Type 2 diabetic patients.     

Twenty-four-hour secretion patterns of luteinizing hormone in mithuns (Bos frontalis)

A 24 h secretion pattern of luteinizing hormone (LH) was not available in mithun (Bos frontalis), a semi-wild ruminant. To characterize the 24 h LH profiles, six female mithun calves (age 7.8 +/- 0.5 months and 102.5 +/- 5.6 kg; group I) and six female mithuns averaging 25.4 months of age and 240 kg (group II) were selected from the National Research Centre on Mithun farm and were maintained in semi-intensive systems. Blood samples collected from all the animals at 30 min intervals for 24h were assayed for plasma LH. Plasma progesterone was also estimated in twice-a-week samples collected for 6-week period preceding each 24h sampling to assess whether any animal had begun ovarian cyclicity. The body weights of all animals were also recorded weekly during the 6-week period. LH patterns consisted of frequent pulses of varying amplitude. Luteinizing hormone pulses occurred at an average frequency of 0.28/h ( approximately 7 pulses/24 h) and 0.15/h ( approximately 3.5 pulses/24 h) for mithuns of groups II and I, respectively, the rate did not differ markedly among mithuns within each group but was significantly different between the groups. Similarly, the magnitude of LH secretory pulses did not vary among mithuns within the group but was significantly higher in group II than in group I animals. In group II, the LH peaks averaged 1.59 and 1.00 ng/ml in mithun having the highest and lowest LH peaks, respectively and the corresponding values for group I mithuns were 0.66 and 0.51ng/ml. Mithun with higher peak LH levels also had higher mean LH concentrations (P<0.05). The mithuns of group II had significantly higher plasma progesterone concentration (0.89 +/- 0.02 ng/ml) than those recorded in group I mithuns (0.26 +/- 0.01 ng/ml). Plasma progesterone profiles suggested that no animal reached puberty. In conclusion, there was higher LH secretion with higher pulsatility and greater amplitude in group II mithuns than exhibited in mithuns of group I and the prepubertal mithuns of group II were in approaching puberty, which were also indicated by their plasma progesterone profiles, critical body weight and age required to attain puberty, in addition to higher pulsatility of LH secretion.     

Efficacy of Lactulose in Cirrhotic Patients with Subclinical Hepatic Encephalopathy

To investigate the role of lactulose in the treatment of cirrhotic patients with subclinical hepatic encephalopathy (SHE), 40 cirrhotic patients, 33 males and 7 females, were included in the study. The diagnosis of SHE was made by quantitative psychometric tests including the number connection test (NCT), figure connection test (FCT) parts A and B, and two performance subtests of Wechsler adult intelligence scale, ie, picture completion (PC) and block design (BD) tests. SHE was diagnosed in 26 (65%) of 40 patients. Of these 26 patients, 14 patients were randomized to treatment group (lactulose 30–60 ml/day for three months, SHE-L) and 12 patients to no treatment group (no lactulose, SHE-NL). Psychometric tests were repeated in all patients in both groups and in six patients with no SHE (group NSHE, N = 14) after three months. The mean scores and number of the abnormal psychometric tests at entry were significantly higher in patients in groups SHE-L and SHE-NL than in patients in group NSHE; however, there was no significant difference between SHE-L and SHE-NL. The mean number of the abnormal psychometric tests decreased in patients in group SHE-L after three months of treatment with lactulose (2.9 ± 0.9 vs 0.8 ± 1.2; P = 0.004); however, there was no change in patients in group SHE-NL after three months (3.7 ± 1.5 vs 3.5 ± 1.3; P = NS). While SHE improved in 8 of 10 patients in group SHE-L, none of the patients in group SHE-NL improved after three months of follow-up (P < 0.001). Two patients in group SHE-NL also developed overt encephalopathy during the study period. We conclude that lactulose treatment in cirrhotic patients with SHE is effective.