Carryover of cigarette smoke effects on hematopoietic cytokines to F1 mouse litters

Neutrophils have been implicated in the pathogenesis of COPD, being recruited into the lung in response to cigarette smoke (CS) inhalation and responsible for the release of proteases and oxidant-producing enzymes, resulting in bronchitis and emphysema. Several hematopoietic cytokines are involved in neutrophil growth and recruitment; however, little is known about the effects of CS on hematopoietic cytokines are transmitted between generations. In the present investigation we evaluate the expression of hematopoietic and proinflammatory cytokines in different organs of female F(0) mice subjected to sub-chronic CS exposure, and in F(1) litters. Virgin female Balb/c mice inhaled either air or air containing CS for 90 days. The specific resistance of the airways (sRaw) was evaluated and, thereafter, the mice were mated with unexposed adult males. The levels of granulocyte-macrophage colony stimulating factor (GM-CSF), granulocyte-colony stimulating factor (G-CSF), interleukin-6 (IL-6), IL-1β and TNF-α mRNA and protein were evaluated in the bone marrow, amniotic fluid and bronchoalveolar lavage fluid (BALF) of F(0) dams at gestation day(14) (gd(14)) and the bone marrow, BALF and lungs of F(0) dams and F(1) littermates at post natal day(21) (pnd(21)). At gd(14), overexpression of GM-CSF, G-CSF and IL-6 mRNA and protein was observed in the bone marrow, amniotic fluid and BALF of F(0) dams. These hematopoietic cytokines were also overexpressed in the lungs of F(1) littermates compared with the control F(1) litters at pnd(21). Lineage-specific hematopoietic growth factors may play an important role in the transmission of neutrophil-associated disease susceptibility across generations.     

Comparative analysis of different DNA-binding drugs for leishmaniasis cure: a pharmacoinformatics approach

Several experiments have been performed to test DNA-binding drugs to cure Leishmania infection. However, there are no details of pharmacoinformatics study. Herein, we have selected a good number of compounds from experimentally verified studies and performed a comparative analysis based on pharmacoinformatics techniques. In silico docking study was performed to observe the molecular level interactions of these known ligands with the DNA receptor by automated computational docking using Glide. A comparison between the calculated interaction energies and in silico ADME/T study was made. In agreement with drug likeness rules, our study suggests that seco-hydroxy-aza-CBI-TMI (compound 4b; GScore, -12.058) is a potential molecule for targeting the DNA to cure leishmaniasis.     

Altered p53 response and enhanced transgenerational transmission of carcinogenic risk upon exposure of mice to betel nut

Alteration of p53 protein level, and possible mutation of the p53 gene during carcinogenesis in mice exposed chronically (P) and transgenerationally to 2mg/ml aqueous extract of betel nut (AEBN) in drinking water, were studied. Exons 5 and 7 of the p53 gene were not mutated under both chronic and transgenerational exposure, but, p53 protein response was altered. In P mice, p53 protein was initially upregulated in comparison to age-matched controls, reaching 2.5 folds in the liver after 6 weeks of exposure. Subsequently, p53 protein declined to control level after 16 weeks, with concomitant preneoplastic nodulation of the liver. After 24 weeks, p53 protein was below control level, and preneoplastic nodules were well-developed. The level of p53 protein in transgenerationally exposed mice remained invariant in comparison to age-matched controls. Liver nodulation was significantly advanced, developing in F1 mice after 8 weeks, F2 mice after 6 weeks and F3 mice after 4 weeks of exposure. Anomalies not observed in P mice, developed in transgenerationally exposed mice, albeit, non-significantly. Thus, AEBN exposure enhanced transgeneration transmission of carcinogenic risk.     

Mental health systems in countries: where are we now?

More than 85% of the world's population lives in 153 low-income and middle-income countries (LAMICs). Although country-level information on mental health systems has recently become available, it still has substantial gaps and inconsistencies. Most of these countries allocate very scarce financial resources and have grossly inadequate manpower and infrastructure for mental health. Many LAMICs also lack mental health policy and legislation to direct their mental health programmes and services, which is of particular concern in Africa and South East Asia. Different components of mental health systems seem to vary greatly, even in the same-income categories, with some countries having developed their mental health system despite their low-income levels. These examples need careful scrutiny to derive useful lessons. Furthermore, mental health resources in countries seem to be related as much to measures of general health as to economic and developmental indicators, arguing for improved prioritisation for mental health even in low-resource settings. Increased emphasis on mental health, improved resources, and enhanced monitoring of the situation in countries is called for to advance global mental health.     

Conflict induced internal displacement in Nepal

Nepal has witnessed a humanitarian crisis since the Maoist conflict began ten years ago. The plight of internally displaced persons (IDPs) in Nepal has received little international attention despite being rated one of the worst displacement scenarios in the world. An estimated 200,000 people have been displaced as a result of the conflict, with the far-western districts of Nepal being the worst affected. Internal displacement has stretched the carrying capacity of several cities with adverse physical and mental health consequences for the displaced. Vulnerable women and children have been the worst affected. The government has adopted a discriminatory approach and failed to fulfil its obligations towards IDPs. Non-governmental organisations and international agencies have provided inadequate services to IDPs in their programmes. Tackling the issues of IDPs requires co-operation between government and development agencies: acknowledging the burden of the problem of IDPs, adequate registration and needs assessment, along with health and nutritional surveys, and development of short-term emergency relief packages and long-term programmes for their assistance.     

Postoperative auras and the risk of recurrent seizures

PURPOSE: Little is known about the prognostic significance of persistent auras following temporal lobe surgery in determining the recurrence of complex partial seizures (CPS) or generalized tonic-clonic seizures (GTCS). METHODS: In a retrospective analysis of temporal lobectomy patients who had preoperative auras associated with CPS or GTCS and who were seizure-free following surgery, the predictive value of auras was assessed at 3 months and 2 years following surgery. Medication use, in relation to the presence of auras, was also assessed. RESULTS: Three hundred and forty-seven patients were seizure-free for 3 months following surgery (247 aura-free, 101 with persistent auras). KM analysis yielded no difference in outcome (p=0.65) and current outcome class was also similar (p=0.99). Patients with persistent auras were somewhat more likely to be on medication at the time of recurrence (p=0.06) and at last follow-up (p=0.09). 224 patients were seizure-free for 2 years following surgery (163 aura-free, 61 with persistent auras). KM analysis yielded no difference in outcome (p=0.86) and current outcome class was also similar (p=0.35). Patients with persistent auras were more likely to be on medication at the time of recurrence (p<0.001) and at last contact (p<0.01). CONCLUSIONS: Auras were not associated with increased risk of recurrence, although increased rates of AED use were seen in these patients. However, any medication effect appears to be quite small, so we consider it reasonable to advise cessation of AEDs in patients with persistent auras who are otherwise seizure-free.     

Mortality rates in geriatric patients with spinal cord injuries

OBJECT: The authors undertook this study to evaluate the incidence of spinal cord injury (SCI) in geriatric patients (> or = 70 years of age) and examine the impact of patient age, extent of neurological injury, and spinal level of injury on the mortality rate associated with traumatic SCI. METHODS: A prospectively maintained SCI database (3481 patients) at a single institution was retrospectively studied for the period from 1978 through 2005. Parameters analyzed included patient age, admission American Spinal Injury Association (ASIA) motor score, level of SCI, mechanism of injury, and mortality data. The data pertaining to the 412 patients 70 years of age and older were compared with those pertaining to the younger cohort using a chi-square analysis. RESULTS: Since 1980, the number of SCI-related hospital admissions per year have increased fivefold in geriatric patients and the percentage of geriatric patients within the SCI population has increased from 4.2 to 15.4%. In comparison with younger patients, geriatric patients were found to be less likely to have severe neurological deficits (greater percentage of ASIA Grades C and D injuries), but the mortality rates were higher in the older age group both for the period of hospitalization (27.7% compared with 3.2%, p < 0.001) and during 1-year follow-up. The mortality rates in this older population directly correlate with the severity of neurological injury (1-year mortality rate, ASIA Grade A 66%, Grade D 23%, p < 0.001). The mortality rate in elderly patients with SCI has not changed significantly over the last two decades, and the 1-year mortality rate was greater than 40% in all periods analyzed. CONCLUSIONS: Spinal cord injuries in older patients are becoming more prevalent. The mortality rate in this patient group is much greater than in younger patients and should be taken into account when aggressive interventions are considered and in counseling families regarding prognosis.