Anatomy,physiology, and pathophysiology of the pedunculopontine nucleus

The pedunculopontine nucleus is composed of cholinergic and non‐cholinergic neurones and is located in the caudal pontomesencephalic tegmentum. Evidence suggests that the nucleus plays a role in the production and control of movement. The nucleus has dense interconnections with the basal ganglia, as well as with other areas of the brain associated with motor control. Electrical stimulation of the pedunculopontine nucleus in the decerebrate cat or rat produces organized locomotor movements. Physiological studies show that the pedunculopontine nucleus modulates its activity in response to locomotion, as well as voluntary arm and eye movements. Degeneration of the pedunculopontine nucleus is seen in post‐mortem brains in humans with Parkinson's disease and Parkinsonian syndromes. In animal models of Parkinson's disease, metabolic changes are seen in the pedunculopontine nucleus, and chemical inhibition or mechanical disruption of the nucleus can produce an akinetic state in animals and man. In this paper we review the literature in support of the suggestion that some of the symptoms of Parkinson's disease are caused by dysfunction of the pedunculopontine nucleus. In accordance with this view, direct stimulation of the nucleus can ameliorate some symptoms of the disease, as demonstrated in both experimental animals and man. © 2008 Movement Disorder Society     

Thalamic field potentials during deep brain stimulation of periventricular gray in chronic pain

Stimulation of the central gray matter areas has been used for the treatment of chronic pain for decades. To better understand the mechanism of action of such treatment we studied the effects of stimulation of the periventricular gray (PVG) on the sensory thalamus in two patients with chronic central pain. In each case, two electrodes were implanted in the PVG (Medtronic 3389) and the ventroposterolateral thalamic nucleus (Medtronic 3387), respectively, under guidance of CT/MRI image fusion. The PVG was stimulated in the frequency range of 2-100 Hz in alert patients while pain was assessed using the McGill-Melzack visual analogue scale. In addition, local field potentials (FPs) were recorded from the sensory thalamus during PVG stimulation. Maximum pain relief was obtained with 5-25 Hz stimulation while 50-100 Hz made the pain worse. This suggests that pain suppression was frequency dependent. Interestingly, we detected low frequency FPs at 0.2-0.4 Hz closely associated with the pain. During 5-25 Hz PVG stimulation the amplitude of this potential was significantly reduced and this was associated with marked pain relief. At the higher frequencies (50-100 Hz) however, there was no reduction in the FPs and no pain suppression. We have found an interesting correlation between thalamic activity and chronic pain. This curious low frequency potential may provide an objective index for quantifying chronic pain, and may hold further clues to the mechanism of action of PVG stimulation.     

Experience,knowledge and attitudes of mental health staff regarding clients with a borderline personality disorder

A survey of mental health staff experience, knowledge and attitudes regarding the management of clients with a diagnosis of borderline personality disorder (BPD) aimed to obtain baseline data to provide direction for developing planned education and determining staff willingness to participate in such training. A 23-item questionnaire was developed and posted to mental health staff in a public Area Mental Health Service in New South Wales ( n = 516). A total of 229 staff completed the questionnaire. Most staff (85%) reported having contact with clients who have a diagnosis of BPD at least once a month or more frequently, with 32% of respondents reporting daily contact. Eighty per cent of respondents found dealing with clients who have a BPD to be moderate to very difficult; 84% of staff felt that dealing with this client group was more difficult than dealing with other client groups. Most staff (82%) believed that, as mental health professionals, they had a role in the assessment, management and referral of clients with BPD, as well as in educating and providing information. Staff readily identified resources which would be helpful to them when working with such clients. It was encouraging to see that the majority of staff (95%) indicated their willingness to gain further education and training in the management of these clients. Although many staff believed they were knowledgeable about and confident in managing these clients, most staff also indicated difficulties posed by these clients and perceived a need for further education and training in this area .     

Involvement of both intrinsic and extrinsic pathways in hepatoprotection of arjunolic acid against cadmium induced acute damage in vitro

Cadmium (Cd) is one of the ubiquitous environmental pollutants and is responsible for various organ pathophysiology including hepatic disorders. It is extremely toxic even in low concentrations and bioaccumulate in organisms. The present study has been carried out to investigate the cytoprotective role of arjunolic acid (AA), a tri terpenoid saponin, against Cd induced oxidative impairment and cell death in murine hepatocytes. Administration of cadmium (30 μM), in the form of chloride (CdCl(2)) for 2h, significantly enhanced the ALT, ALP and LDH leakage, increased reactive oxygen species (ROS) production, reduced hepatocytes viability and altered the antioxidant status of hepatocytes by reducing intracellular GSH level, anti-oxidant enzymes activity and increasing intracellular GSSG and lipid peroxidation. Evidence for Cd-induced nature of cell death was sought by flow cytometric analysis. Signal transduction studies revealed that Cd markedly increased the levels of caspase-9, -8, -3, Fas and Bid, decreased mitochondrial membrane potential, enhanced cytochrome c release in the cytosol, disturbed the Bcl-2 family protein balance, cleaved PARP protein and ultimately led to apoptotic cell death. Results showed that Cd could trigger both intrinsic and extrinsic apoptotic pathways. In addition, Cd markedly increased NF-κB nuclear translocation in association with IKKα/β phosphorylation and IκBα degradation. Simultaneous treatment with AA (200 μM), however, reduced Cd-induced oxidative stress, attenuated the nuclear translocation of NF-κB and protects the hepatocytes from Cd-induced apoptotic death. Combining, data suggest that Cd-induced hepatic dysfunction and apoptosis might be supported by the ROS formation and mediated via the activation of NF-κB. AA treatment, on the other hand, reduced Cd-induced oxidative stress, attenuated the activation of NF-κB and mitochondrion-dependent and independent apoptotic signaling pathways.     

Pattern of mental illness on substance abusers

The aim of this study was to investigate mental illnesses among the substance abuse dependent populations. A total of 1076 substance abusers were recruited from the Outpatient Department of the Central Drug Addiction Treatment Center, Tejgaon, Dhaka from July 2008 to June 2009. They sought detoxification therapy voluntarily at this centre. The research participants were selected consecutively following the defined selection criteria. Research instruments were interviewer-administered questionnaire and standard mental state examination scales. Of the 1076 substance abusers, 82.6% had been using heroin currently and rest of them used phensedyl followed by injection drugs and cannabis with a period ranged 2-30 years. Results showed that 91.3% of the substance abusers had been suffering from insomnia and 75.0% had altered food habit. About 49.0% showed disturbed behaviors and 45.2% had been suffering from sexual dysfunctions. Around 32.0% of the substance abusers had been suffering from nonspecific generalized anxieties and 72.7% were found in abnormal mood/affects. A striking finding was that 7.3% of the substance abusers had been suffering from perceptual and/or thought disturbances. In conclusion, 7.3%-92.5% of the substance abusers had been suffering from mental illnesses. Insomnias, decreased intake of food and taste preference, irritable mood/affects, loss of interest in sex and non-specific anxieties were highly prevalent among them. Medical management and altering lifestyle are still the only applicable way to control this human catastrophe.     

Drug therapy in autism: a present and future perspective

Autism is a neurodevelopmental disorder, with a multifactorial etiology, characterized by severe abnormalities in communications, social awareness and skills, and the presence of restrictive and stereotyped patterns of behaviors. It is traditionally considered a “static” encephalopathic disorder without any specific cure and few effective biomedical interventions. There are various factors which are involved in the etiopathogenesis of autism or autism spectrum disorder (ASD) such as impaired immune responses, neuroinflammation, abnormal neurotransmission, oxidative stress, mitochondrial dysfunction, environmental toxins and stressors. The autism is often associated with a number of genetic disorders such as fragileXsyndrome, tuberous sclerosis, epilepsy and Down syndrome. The recent approaches to autism treatment included various non-pharmacological and pharmacological therapy such as food supplementation, detoxification, treatment of neuroinflammation, immunologic treatments and psychotropic medications, which are found to be effective in treating various behavioral symptoms of autism. In current practice, there is no curative treatment for autism but the recommended treatment for autism involves educational therapies: speech therapy, sensory integration therapy, auditory therapy. There are classes of different pharmacological agents which are found to be effective in improving behavioral symptoms of ASD such as neurotransmitter reuptake inhibitors (fluoxetine), tricyclic antidepressants (imipramine), anticonvulsants (lamotrigine), atypical antipsychotics (clozapine), acetylcholinesterase inhibitors (rivastigmine), etc. New classes of drugs with novel mechanisms of action should be there so that this disorder will become less prevalent in the future.     

Spectrum of Acute Viral Hepatitis in Southern India

Background

The incidence of hepatitis-A among adults in India is on the decline as majority develops protective immunity to it by late adolescence. Most of these studies are from northern India. Clinical spectrum of sporadic acute viral hepatitis from southern India has not been well documented.

Methods

A prospective hospital based study was conducted in a large military hospital in southern India. 224 consecutive patients with acute viral hepatitis were studied for their presentation, etiology and clinical features.

Result

Hepatitis-E was detected in 102 (45.4%), hepatitis A in 74 (33%) and hepatitis B in 28 (12.5%) patients. Acute hepatitis C was detected in two patients. 15 patients had a mixed infection. Hepatitis A constituted 41.2% and 31.3% of all cases in the age groups 11-20 and 21-30 years respectively. Cholestasis was present in 68 (30.4%) patients with hepatitis E accounting for most (61.8%) cases. There were four (1.8%) cases of acute liver failure. Two cases were due to hepatitis E and one case each was due to hepatitis A and hepatitis B. A relapsing course was seen in four cases due to hepatitis-A.

Conclusion

Hepatitis A remains a significant cause of sporadic acute viral hepatitis in young adults in southern India.Key Words: Viral hepatitis, Hepatitis A