Induction of Tolerance to Non Steroidal Anti Inflammatory Drugs Might Be an Alternative Therapeutic in the Painful Crisis of Sickle Cell Disease

Background and Aims: In Ivoirian’s school, the management of vaso-occlusive painful crisis in sickle cell disease requires non steroidal anti inflammatory drugs (NSAIDs). Although their effectiveness, these drugs may be accompanied by intolerance reactions. When these occur, no codified alternative therapeutic seems to be used to our knowledge. Authors aimed to evaluate the induction of tolerance to NSAIDs as an effective alternative therapeutic. Methods: 22 patients (15 men and 7 women aged from 12 to 39 years with mean age: 22.41 ± 7.88) suffering from vaso-occlusive painful crisis were enrolled. They were known to have a history of sickle cell disease and at least one episode of adverse reactions following the Ibuprofen or Diclofenac intake. A rapid protocol of oral challenge was used in patients to induce tolerance to NSAIDs. The first day, initial doses (8.82 mg for Ibuprofen and 2.20 mg for Diclofenac) were given and gradually increased at intervals of 1 hour over a total period of 6 hours. On the second and third days, the therapeutic dose has been orally administrated with an interval of 6 hours over a period of 12 hours. Results: Despite of some cases of failure that might be related to the severity of symptoms or possible patho-physiological mechanism, more than 80% of patients have successfully tolerated Diclofenac and Ibuprofen. Conclusion: This experience appears to be the first in our context. It might be used as a solution in the lack of alternative therapeutic in the management of vaso-occlusive painful crisis of sickle cell disease as well as in other diseases such as HIV infection where patients often develop intolerance to none alternative antibiotics.

Effects of chronic therapy with non-steroideal antinflammatory drugs on gastric permeability of sucrose: A study on 71 patients with rheumatoid arthritis

AIM： To evaluate the gastric permeability after both acute and chronic use of non-steroidal anti-inflammatory drugs （NSAIDs） and to assess the clinical usefulness of sucrose test in detecting and following NSAIDs-induced gastric damage mainly in asymptomatic patients and the efficacy of a single pantoprazole dose in chronic users. METHODS： Seventy-one consecutive patients on chronic therapy with NSAIDs were enrolled in the study and divided into groups A and 13 （group A receiving 40 mg pantoprazole daily, group B only receiving NSAIDs）. Sucrose test was performed at baseline and after 2, 4 and 12 wk, respectively. The symptoms in the upper gastrointestinal tract were recorded. RESULTS： The patients treated with pantoprazole had sucrose excretion under the limit during the entire follow-up period. The patients without gastroprotection had sucrose excretion above the limit after 2 wk, with an increasing trend in the following weeks （P = 0.000）. A number of patients in this group revealed a significantly altered gastric permeability although they were asymptomatic during the follow-up period. CONCLUSION： Sucrose test can be proposed as a valid tool for the clinical evaluation of NSAIDs-induced gastric damage in both acute and chronic therapy. This tecnique helps to identify patients with clinically silent gastric damages. Pantoprazole （40 mg daily） is effective and well tolerated in chronic NSAID users .

Microvessel density is a prognostic marker of human gastric cancer

AIM: To investigate whether microvessel density (MVD) is related with prognosis in gastric cancer patients, and the expression of cyclooxygenase-2 (COX-2) and vessel endothelial growth factor (VEGF) so as to determine the possible role of COX-2 and VEGF in gastric cancer angiogenesis.METHODS: Forty-seven formalin-fixed paraffin-embedded tissue samples of gastric cancer were evaluated for COX-2, VEGF by immunohitochemical staining. To assess tumor angiogenesis, MVD was determined by immunohitochemical staining of endothelial protein factor Ⅷ-related antigen. The relationship among COX-2 and VEGF expression, MVD, and clinicopathologic parameters was analyzed. RESULTS: Among the 67 samples, high MVD was significantly associated with lymph node metastasis and poor survival. Multivariate survival analysis showed that MVD value and lymph node metastasis were independent prognostic factors. The expression rate of COX-2 and VEGF was significantly higher than that of the adjacent tissues. COX-2 and VEGF expression in gastric cancer was significantly correlated with tumor differentiation and depth of invasion, but not with survival. The mean MVD value of COX-2 or VEGF positive tumors was higher than that of COX-2 or VEGF negative tumors. A significant correlation was found between the expressions of COX-2and VEGF. CONCLUSION: MVD may be one of the important prognostic factors for gastric cancer patients. COX-2 and VEGF may play an important role in tumor progression by stimulating angiogenesis. VEGF might play a main role in the COX-2 angiogenic pathway. The inhibition of angiogenesis or COX-2, VEGF activity may have an important therapeutic benefit in the control of gastric cancer.

A survey of analgesic and anti-inflammatory drug prescription for oral implant surgery

Aim:This study was conducted to determine the preferred analgesic and anti-inflammatory drugs prescribed by oral implantologists in India.Methods:A structured questionnaire was distributed to 332 dentists to gather information regarding their prescription habits for analgesics and anti-inflammatory drugs.Frequency distributions were computed by type of drug being prescribed and the protocol followed.Results:Analysis of data showed that majority of dentists(85.8%,n=285)prescribed conventional non-steroidal anti-inflammatory drugs(NSAIDs)for implant surgery.The most common prescription was ibuprofen with paracetamol combination(32.2%,n=107)followed by diclofenac(20.2%,n=67).Most dentists reported prescribing different NSAIDs for the same procedure in different patients(64.7%,n=215).Only,35.5%(n=118)followed the peri-operative protocol.Adjunctive prescription of steroids was done by only 33.7%(n=112).Conclusion:Our study illustrates that the general trend of analgesic and anti-inflammatory drug prescription for dental implant surgery among Indian dentists is mostly in accordance with the guidelines for pain management worldwide.However,it is noteworthy that a few dentists do prescribe drugs not primarily indicated for dental pain management and use widely varying protocols for the same.Therefore,in order to avoid potential complications,it is essential to raise awareness of among the dental practitioners of the appropriate indications and dosage regimen of specific drugs.

Neuroinflammation and excitatory symptoms in bipolar disorder

Neuroinflammation has been proposed as a strong biological factor underlying the development of neuropsychiatric diseases.A role for dysregulation of the immune system was initially suggested in depressive disorders and subsequently extended to other illnesses,including bipolar disorder(BD).Indeed,there is growing evidence confirming the presence of a generalized pro-inflammatory state in BD patients,involving alterations in cytokine,acute-phase proteins,and complement factor secretion,white blood cell differentiation,microglial activation,arachidonic acid signaling pathways,and increased oxidative stress markers.Medications commonly used to treat BD,such as lithium,antiepileptics and antipsychotics,show some immunoregulatory activity both in vitro and in vivo.The aim of our study was to review the role of different inflammatory mechanisms,specifically in the development of excitatory symptoms,via a systematic PubMed search of the literature.Despite the high variability of results among studies,we found evidence indicating specific alterations of the inflammatory response during manic and mixed states of BD.These findings may help to clarify some of the complex mechanisms underlying the development of excitatory symptoms and suggest a potential role for drugs targeting the inflammatory system as new therapeutic options.