Neuroprotective effect of combination of poly (ADP-ribose) polymerase inhibitor and antioxidant in middle cerebral artery occlusion induced focal ischemia in rats

Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research, Punjab, India We have investigated the neuroprotective potential of combination of poly (ADP-ribose) polymerase inhibitor (nicotinamide or 3-aminobenzamide) and antioxidant (melatonin) in middle cerebral artery occlusion (MCAo) induced focal ischemia in rats. MCAo of 2 h followed by 22 h reperfusion produced large volume of cerebral infarction (mean +/- SEM 211.38 +/- 8.35 mm3), volume of edema (60 +/- 2 mm3) and neurological deficits (4.45 +/- 0.25). Combination of nicotinamide (500 mg kg(-1), i.p.) and melatonin (10 mg kg(-1), i.p.) significantly decreased infarct volume to 48 +/- 2.58 mm3 as compared to their individual drug (nicotinamide 76 +/- 12.49mm3, melatonin 76.17 +/- 1.24 mm3). A significant improvement was observed in edema volume and neurological deficits with this combination. Combination of 3-aminobenzamide (20 mg kg(-1), i.p.) and melatonin (10 mg kg(-1), i.p.) also produced similar reduction in infarction, edema and neurological score. These results indicate that the combination of poly (ADP-ribose) polymerase inhibitor and antioxidant produce enhanced neuroprotection. Clinical availability and wide therapeutic margin of nicotinamide and melatonin make them a promising drug combination for clinical evaluation in stroke patients.     

Neuroacanthocytosis misdiagnosed as Huntington's disease: a case report

A patient with the typical features of neuroacanthocytosis is reported. Chorea, tics, personality changes and caudate atrophy on cranial MRI resulted in an erroneous diagnosis of Huntington's disease elsewhere. Attention to other features viz., absence of ocular motility disturbances, amyotrophy, areflexia, EMG evidence of axonopathy, raised serum creatinine phosphokinase (CPK) levels and the typical erythrocytic acanthocytosis enabled us to establish the correct diagnosis. The typical features of the disease as seen in the patient are discussed. In view of the implications for genetic counseling, careful clinical and laboratory evaluation is always warranted to exclude neuroacanthocytosis in all suspected cases of Huntington's disease.     

Keith Edwards score for diagnosis of tuberculosis

Objective : To evaluate the applicability of Keith Edwards scoring system for the diagnosis of childhood tuberculosis.Methods. One hundred and one children aged 2 months to 12 years who fulfilled the inclusion criteria were evaluated with Keith Edwards score. The diagnosis of tuberculosis by Keith Edwards score and the definitive reference were compared.Results. Among the 65 children diagnosed as having tuberculosis by the definitive reference, 59 had a Keith Edwards score of >7. Four children had a score of >7 but were not suffering from tuberculosis. The sensitivity and specificity of this score have been found to be 91% and 88% respectively.Conclusion. In select population with indicative clinical features, Keith Edwards score can be a definitive guideline for the diagnosis of childhood tuberculosis. However, more studies are required for the validation of this clinical score before it can be used as a definitive diagnostic reference standard for tuberculosis.     

Oral miltefosine treatment in children with mild to moderate Indian visceral leishmaniasis

BACKGROUND: Miltefosine is the first oral drug with demonstrable success in treating visceral leishmaniasis in adults. Because approximately one-half of the visceral leishmaniasis patients worldwide are children, we performed a Phase I/II dose ranging study in the pediatric population in India. METHODS: Thirty-nine (39) children (defined as < 12 years of age) with visceral leishmaniasis demonstrated by parasites in splenic aspirates, were treated with oral miltefosine daily for 28 days: 21 patients received 1.5 mg/kg/day (Group A); and 18 patients received 2.5 mg/kg/day (Group B). About one-half of these children had failed prior antileishmanial treatment. RESULTS: All patients were parasitologically negative and symptomatically improved by the end of therapy on Day 28 of therapy; the initial parasitologic cure rate was 100%. Two patients in each treatment group relapsed with fever, splenomegaly and parasite-positive splenic aspirates by the end of the 6-month follow-up. The per protocol final clinical cure rate was 19 of 21 = 90% in Group A and 15 of 17 = 88% in Group B. Miltefosine was well-tolerated. As per the adult experience, gastrointestinal adverse events were seen: 33 and 39% of children experienced vomiting and 5 and 17% experienced diarrhea in Groups A and B, respectively, but all episodes were mild to moderate in severity and commonly lasted <1 day without symptomatic treatment. CONCLUSION: Oral miltefosine was safe and approximately 90% effective in this initial clinical trial of childhood visceral leishmaniasis.     

Neonatal spinal cord injury

Neonatal spinal cord injury (SCI) is well described in the literature, though its diagnosis is often delayed or missed in the neonatal period. We present a neonate who was referred with upper gastrointestinal bleed and a diagnosis of spinal cord injury was subsequently made clinically and confirmed radiologically.