Drug and Alcohol Rehabilitation: Psychiatric, Somatic and Other Functional Gastrointestinal Disorders in Patients With Irritable Bowel Syndrome at a Tertiary Care Center.

Psychiatric, somatic and other functional gastrointestinal disorders in patients with irritable bowel syndrome at a tertiary care center.

Filed under: Drug and Alcohol Rehabilitation

J Neurogastroenterol Motil. 2012 Jul; 18(3): 324-31
Singh P, Agnihotri A, Pathak MK, Shirazi A, Tiwari RP, Sreenivas V, Sagar R, Makharia GK

To study the prevalence of somatic and psychiatric co-morbidities in the patients of irritable bowel syndrome (IBS) and to assess the quality of life (QOL) of these patients.One hundred and eighty-four IBS patients and 198 controls were included. Diagnosis of IBS, its sub-classification and assessment of other functional gastrointestinal disorders (FGIDs) was made on basis of Rome III criteria. Severity of IBS was assessed using IBS severity scoring system. Psychiatric evaluation was done using Patient Heath Questionnaire. QOL was evaluated using WHO QOL-BREF.One hundred and forty-seven (79.9%) and 158 (85.9%) patients with IBS had at least one other FGID or at least one somatic co-morbidity, respectively. Higher number of patients had at least one psychiatric co-morbidity compared to controls (79.9% vs 34.3%; P < 0.001). Major depressive syndrome (47.3% vs 5.1%; P < 0.001), somatoform disorder (50% vs 14.6%; P < 0.001) and panic syndrome (44% vs 11.6%; P < 0.001) were more common in IBS than controls. Only 14 (7.6%) patients were receiving drug treatment for their psychiatric illness. Severe IBS symptoms were present in significantly higher number of patients with constipation predominant IBS than diarrhea predominant IBS. Those with severe disease had higher prevalence of psychiatric (95.1%) and somatic (96.7%) co-morbidities compared with mild disease. QOL of IBS patients was significantly lower in all four domains compared to controls. Presence of at least one other FGID was significantly associated with presence of one or more psychiatric co-morbidity (P < 0.001).Majority of IBS patients presenting to a tertiary care center had associated psychiatric, somatic co-morbidities and reduced QOL. Very few of them received specific psychiatric treatment. HubMed – drug


Chiral cyclohexane 1,3-diones as inhibitors of mutant SOD1-dependent protein aggregation for the treatment of ALS.

Filed under: Drug and Alcohol Rehabilitation

ACS Med Chem Lett. 2012 May 22; 3(7): 584-587
Zhang Y, Benmohamed R, Zhang W, Kim J, Edgerly CK, Zhu Y, Morimoto RI, Ferrante RJ, Kirsch DR, Silverman RB

Cyclohexane 1,3-diones were identified as a class of molecules exhibiting a protective effect against mutant SOD1 induced toxicity in PC-12 cells, but an optimized analogue had little or no effect on life extension in the G93A SOD1 mouse model for amyotrophic lateral sclerosis (ALS). Additional testing showed that these compounds were inactive in neurons and further analogue synthesis was carried out to identify compounds with neuronal activity. Starting from two racemic derivatives that were active in cortical neurons, two potent analogues (1b and 2b) were resolved, which were protective against mutant SOD1 induced toxicity in PC-12 cells. Both compounds were found to be active in cortical neurons and presented good ADME profiles in vitro. On the basis of these results, an ALS mouse trial with 1b was carried out, which showed slightly greater life extension than the FDA-approved ALS drug riluzole, thereby validating cyclohexane 1,3-diones as a novel therapeutic class for the treatment of ALS.
HubMed – drug


Discovery of Imidazoquinolines with Toll-Like Receptor 7/8 Independent Cytokine Induction.

Filed under: Drug and Alcohol Rehabilitation

ACS Med Chem Lett. 2012 Jun 14; 3(6): 501-504
Shi C, Xiong Z, Chittepu P, Aldrich CC, Ohlfest JR, Ferguson DM

Toll-like receptors (TLRs) are key targets in the design of immunomodulating agents for use as vaccine adjuvants and anticancer treatments. The imidazoquinolines, imiquimod and resiquimod, have been shown to activate TLR-7 and -8 which in turn induce cytokine production as part of the innate immune response. Herein, we report the synthesis and discovery of a C7-methoxycarbonyl derivative of imiquimod that stimulates cytokine production but is devoid of TLR-7/8 activity. Data is presented that shows this analog not only induces IL-12p40 and TNF production, similar to that of imiquimod and resiquimod, but greatly enhances the production of IL-1?, a key cytokine involved in activation of CD4 T cells. It is further demonstrated that TLR-7/8 activation can be recovered by the addition of a C2-alkyl substituent to this newly discovered analog. The results support the existence of an alternative mechanism of action by which imidazoquinolines can stimulate cytokine production.
HubMed – drug


Progressive effect of beta amyloid peptides accumulation on CA1 pyramidal neurons: a model study suggesting possible treatments.

Filed under: Drug and Alcohol Rehabilitation

Front Comput Neurosci. 2012; 6: 52
Culmone V, Migliore M

Several independent studies show that accumulation of ?-amyloid (A?) peptides, one of the characteristic hallmark of Alzheimer’s Disease (AD), can affect normal neuronal activity in different ways. However, in spite of intense experimental work to explain the possible underlying mechanisms of action, a comprehensive and congruent understanding is still lacking. Part of the problem might be the opposite ways in which A? have been experimentally found to affect the normal activity of a neuron; for example, making a neuron more excitable (by reducing the A- or DR-type K(+) currents) or less excitable (by reducing synaptic transmission and Na(+) current). The overall picture is therefore confusing, since the interplay of many mechanisms makes it difficult to link individual experimental findings with the more general problem of understanding the progression of the disease. This is an important issue, especially for the development of new drugs trying to ameliorate the effects of the disease. We addressed these paradoxes through computational models. We first modeled the different stages of AD by progressively modifying the intrinsic membrane and synaptic properties of a realistic model neuron, while accounting for multiple and different experimental findings and by evaluating the contribution of each mechanism to the overall modulation of the cell’s excitability. We then tested a number of manipulations of channel and synaptic activation properties that could compensate for the effects of A?. The model predicts possible therapeutic treatments in terms of pharmacological manipulations of channels’ kinetic and activation properties. The results also suggest how and which mechanisms can be targeted by a drug to restore the original firing conditions.
HubMed – drug



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Drug Treatment Centers Florida Provide Effectiveness Where Others Have Failed

Filed under: Drug and Alcohol Rehabilitation

They provide the most innovative drug and alcohol treatment, with an astonishing success rate, which is a result of their treatment modality that genuinely works. They have an experienced, knowledgeable and understanding multidisciplinary team that …
Read more on Connectus.net (press release)


Dr. Kevin Sabet's Kinder Gentler Drug War

Filed under: Drug and Alcohol Rehabilitation

Heard any calls to set quotas on how much Budweiser can be manufactured, like the DEA restricts scheduled drugs? How about removing funny sexy beer ads from TV? How about mandatory 12-month alcoholic rehab for any drinker who commits a crime?
Read more on Huffington Post


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