Plasma level distribution, effect and toxicity of antiepileptic drugs among Ethiopian epileptics

Plasma phenytoin and phenobarbitone levels were estimated in 123 adult Ethiopian epileptics by gas-liquid chromatography. Thirty four (38.2%) of the patients on phenytoin, and 52 (52%) of those on phenobarbitone, had plasma levels in the conventional therapeutic ranges of 10-20 micrograms/ml and 10-30 micrograms/ml respectively. Of the 89 patients who were taking phenytoin either singly or combined with phenobarbitone, motor disturbances (ataxia and nystagmus) were seen in 31 (34.8%) and dysmorphic and idiosyncratic side effects including gum hypertrophy, hirsutism, acne and skin rash in 37 (41.6%). Subnormal serum calcium levels were noted in 15 (30.6%) and high alkaline phosphatase was found in 13 (26.5%). Phenobarbitone was found to be an effective anticonvulsant (78.1% seizure control rate), with adverse effects of sedation and intellectual depression. Seizure control was achieved in 77.1% of patients on a single drug as opposed to 55.6% on combination of phenytoin and phenobarbitone (p less than 0.05). The overall seizure control rate was 66%.     

Recombinant alpha2(IV)NC1 domain inhibits tumor cell-extracellular matrix interactions, induces cellular senescence, and inhibits tumor growth in vivo

Cellular interaction with the extracellular matrix is thought to be a critical event in controlling angiogenesis and tumor growth. In our previous studies, genetically distinct noncollagenous (NC) domains of type-IV collagen were shown to interact with integrin receptors expressed on the surface of endothelial cells. Moreover, these NC1 domains were shown to inhibit angiogenesis in vivo. Here, we provide evidence that a recombinant form of the alpha2(IV)NC1 domain of type-IV collagen could bind integrins alpha1beta1 and alphavbeta3 expressed on melanoma cells and inhibit tumor cell adhesion in a ligand-specific manner. Systemic administration of recombinant alpha2(IV)NC1 domain potently inhibited M21 melanoma tumor growth within full thickness human skin and exhibited a dose-dependent inhibition of tumor growth in nude mice. Interestingly, alpha2(IV)NC1 domain enhanced cellular senescence in tumor cells in vitro and in vivo. Taken together, these results suggest that recombinant alpha2(IV)NC1 domain is not only a potent anti-angiogenic reagent, but it also directly impacts tumor cell behavior. Thus, alpha2(IV)NC1 domain represents a potent inhibitor of tumor growth by impacting both endothelial and tumor cell compartments.     

IFN‐γ against the 38‐kDa antigen of Mycobacterium tuberculosis discriminates pulmonary tuberculosis from infection and infection from exposure: evidence from a study of human population in a high endemic setting

Mycobacterium tuberculosis (Mtb) 38‐kDa antigen is an immunogenic lipoprotein that induces strong T‐cell responses in experimental animals. However, there is limited information on the role of this antigen in human population. In this article, we present the dynamics of pro‐inflammatory (IFN‐γ and TNF‐α) and anti‐inflammatory cytokine (IL‐10) against the 38 kDa in cohorts of pulmonary TB (PTB) patients, household contacts (HHCs), and community controls (CCs) in a high endemic setting. Whole blood assay was used to determine the levels of cytokines in 149 patients, 149 HHCs, and 68 CCs at baseline, 6 months, and 12 months. At baseline, the level of IFN‐γ was significantly (p < 0.0001) higher in CCs and HHCs than in untreated patients. CCs had significantly (p < 0.05) higher level of IFN‐γ than HHCs. There was no significant difference between treated and untreated patients, and there was no significant change in HHCs over 12 months. At baseline, the levels of IL‐10 and TNF‐α were significantly (p < 0.0001) higher in patients than in HHCs and CCs. No significant change was observed between treated patients and untreated patients and HHCs over time. The study shows that IFN‐γ against the 38 kDa discriminates clinical TB from infection and infection from exposure, suggesting its potential for immune protection and diagnosis.     

What We Know and Don’t Know About Mental Health Problems Among Immigrants in Norway

Mental health problems have been regarded as one of the main public health challenges of immigrants in several countries. Understanding and generating research-based knowledge on immigrant health problems is highly relevant for planning preventive interventions, as well as guiding social and policy actions. This review aims to map the available knowledge on immigrants’ mental health status and its associated risk factors in Norway. The reviewed literature about mental health problems among immigrant populations in Norway was found through databases, such as PUBMED, EMBASE, PsychINFO and MEDLINE. About 41 peer-reviewed original articles published since 1990s were included. In the majority of the studies, the immigrant populations, specifically adult immigrants from low and middle income countries, have been found with a higher degree of mental health problems compared to Norwegians and the general population. Increased risk for mental illness is primarily linked to a higher risk for acculturative stress, poor social support, deprived socioeconomic conditions, multiple negative life events, experiences of discrimination and traumatic pre-migration experiences. However, research in this field has been confronted by a number of gaps and methodological challenges. The available knowledge indicates a need for preventive interventions. Correspondingly, it strongly recommends a comprehensive research program that addresses gaps and methodological challenges.     

Effects of acrylic resin monomers on porcine coronary artery reactivity

The purpose of the present investigation was to assess the reactivity of porcine coronary arteries under in vitro conditions following their exposure to methyl methacrylate (MMA) and hydroxyethyl methacrylate (HEMA) monomers. Confirming previous studies using rat aortas, both MMA and HEMA induced acute/direct relaxation of coronary ring preparations, which was partly dependent on the endothelium. With prolonged tissue exposure, both monomers caused time- and concentration-dependent inhibition of receptor-mediated contraction of the vascular smooth muscle caused by prostaglandin F_2∝ (PGF_2∝), with HEMA causing more inhibition than MMA. Hydroxyethyl methacrylate, but not MMA, also produced impairment of non-receptor-mediated contraction of the coronary smooth muscle induced by KCl. On the other hand, neither HEMA nor MMA altered relaxation of the smooth muscle produced by the direct-acting pharmacological agent, sodium nitroprusside (SNP). While exposure to HEMA impaired endothelium-dependent vasorelaxation caused by bradykinin (BK), MMA markedly enhanced this endothelial-mediated response of the arteries. The enhanced endothelial response produced by MMA was linked to nitric oxide (NO) release. In conclusion, with prolonged tissue exposure, MMA causes less pronounced effects/adverse consequences on coronary smooth muscle function relative to the effect of HEMA, while enhancing vasorelaxation associated with release of NO from the endothelium. Accordingly, MMA-containing resin materials appear to be safer for human applications than materials containing HEMA.     

Association of ABO blood group and P. falciparum malaria related outcomes: a cross-sectional study in Ethiopia

Studies elucidate conflicting results about the relationships between ABO blood groups and Plasmodium infection outcomes in humans. This study examined association between ABO blood group and Plasmodium falciparum (P. falciparum) malaria related outcomes among 1065 malaria suspected febrile patients who attended Dore Baafano Health Center, southern Ethiopia, between December, 2010 and February, 2011. Blood specimens were collected and examined for malaria using Giemsa-staining, while stool specimens were examined for helminth infections using Kato-Katz method. Haemoglobin level and blood group were determined using hemocue machine and antisera hemagglutination test, respectively. Clinical data were also collected for the patients. Among the study participants, the proportion of O, A, B and AB blood groups were 40.1%, 30.1%, 29.0% and 14.3%, respectively, and P. falciparum malaria cases in the corresponding blood groups were 14.8%, 14.0%, 13.4% and 15.7%. The odds of non-severe P. falciparum malaria were not significantly different between individuals of blood group A versus O or B versus O or AB versus O. Mean haemoglobin concentration was significantly lower in P. falciparum infected blood type A individuals compared to P. falciparum infected blood type O (β=-1.25, 95% CI=-2.31 to -0.19) or non-A (β=-1.27, 95% CI=-2.23 to -0.32) individuals. The odds of P. falciparum malaria related anaemia was about three times higher in individuals with blood type A compared to those with blood type O (adjusted OR=2.82, 95% CI=1.05-7.56) or non-A individuals (adjusted OR=2.84, 95% CI=1.15-7.01). However, mean P. falciparum density did not significantly differ among patients according to their blood groups. In conclusion, individuals with blood group A had higher risk of anaemia compared to those with O and non-A phenotypes among P. falciparum malaria patients. However, there is a need to investigate the mechanism.