Concurrent Hepatotoxicity and Neutropenia Induced by Clozapine.

Clozapine is known as one of the atypical antipsychotics which is placed in the second line of medical treatment for schizophrenia due to its hematologic complications. It is used in cases of resistance to treatment. Some side effects of clozapine include leukopenia, granulocytopenia, fever, hepatotoxicity, sedation, dizziness, hypotension, weight gain, constipation, and seizure. Neutropenia and hepatotoxicity have been separately reported after taking atypical antipsychotics, including clozapine. However, simultaneous occurrence of these two complications is rare and has not been reported with clozapine use. This study reports a case of concurrent hepatotoxicity and neutropenia induced by clozapine. The patient was a 58-year-old man who started taking clozapine for the first time in March 2017, about seven weeks before his recent admission, because of a history of treatment-resistant schizophrenia. He had been referred to the emergency department of a general hospital with symptoms of weakness, lethargy, fever, and chills. The laboratory results showed neutropenia with a frequency of 352 × 103 (17.5%) and hepatotoxicity with alanine transferase (ALT) = 139 u/L, aspartate transferase (AST) = 214 u/L, total bilirubin = 11.5 mg/dL, and direct bilirubin = 9.3 mg/Dl, caused by taking clozapine. The symptoms were attenuated within eight days after discontinuation of clozapine. Moreover, the patient's para-clinical complications including neutropenia, and raised transaminases and bilirubin returned to normal. It was concluded that clozapine can simultaneously cause neutropenia and hepatotoxicity; physicians are recommended to be aware of this issue to prevent mortality through appropriate and timely diagnosis.

Cloning and Expression of B. mellitensis bp26 Gene in Lactococcus lactis as a Food Grade Vaccine.

BACKGROUND: Brucellosis is still an important health problem in under developing countries and researches for finding efficient vaccine are going on. Brucella melitensis (B. mellitensis) bp26 gene is a good candidate for brucellosis vaccine and investigations showed that Lactococcus lactis (L. lactis) with several positive characteristic are attractive for protein expression as a live delivery vectors. These fast growing bacteria need no aeration, are easy to handle, have no exotoxin, endotoxin and protease, so the cost of culturing is inexpensive. METHODS: B. mellitensis bp26 gene was cloned in food grade pNZ 8149 vector and expressed in L. lactis NZ 3900. RESULTS: Results showed that we can produce a food-grade recombinant L. lactis producing the B. melitensis BP26 protein. CONCLUSION: In this study, for Future evaluation about ability of L. lactis as a live delivery vector, a food-grade recombinant L. lactis producing the B. melitensis BP26 protein was produced.

Alterations in oxidative stress markers and its correlation with clinical findings in schizophrenic patients consuming perphenazine, clozapine and risperidone.

BACKGROUND AND OBJECTIVE: Today, the role of oxidative stress in development of schizophrenia has gained attention. Also, some atypical antipsychotic agents showed antioxidant properties. Therefore, in this study, we evaluated the level of oxidative stress parameters between patients treated with perphenazine, clozapine and risperidone and their relationship with schizophrenia symptoms' severity. MATERIALS AND METHODS: This was a descriptive study on 100 patients with chronic schizophrenia. Patient selection was done based on the DSM-IV-TR criteria for at least 3 months regular use of clozapine or risperidone or perphenazine and a minimum period of 2 years of schizophrenia. Ten ml of patient's blood samples were used to assess serum levels of glutathione (GSH), protein carbonyl, lipid peroxidation (LPO), superoxide dismutase (SOD) and Ferric Reducing Ability of Plasma (FRAP). Also, the severity of symptoms was assessed with the positive and negative syndrome scale (PANSS scale). P-values of less than 0.05 were considered significant. RESULTS: The results showed a significant difference between clozapine and risperidone with perphenazine in all subscales of PANSS. Also, there was a positive correlation between MDA and PANSS all subscales in risperidone and perphenazine groups and a negative correlation between MDA and PANSS in all subscales in the clozapine group. Serum level of GSH and negative symptoms in patients receiving clozapine showed a negative correlation. The results also represented that clozapine significantly increased SOD levels in comparison to perphenazine and risperidone and reduced LPO in comparison to perphenazine and risperidone, While the protein carbonyl level did not show a significant difference between three groups (p-value = 0.8). CONCLUSION: This study showed that clozapine, as an atypical antipsychotic agent, has significant antioxidant effects compared to risperidone and perphenazine. Especially, it increased SOD and GSH levels and reduced LPO in patients with schizophrenia. Therefore, clozapine's antioxidant effect may be contributive to improving negative symptoms of schizophrenic patients.

Disease-Related Variables and Depression Among Iranian Patients with Parkinson Disease.

BACKGROUND: The factors affecting the correlation between Parkinson disease (PD) and depression have remained unclear. OBJECTIVES: We assessed the prevalence of depression among patients with PD and the association between PD-related variables and depression severity. PATIENTS AND METHODS: This is a cross-sectional study performed in Kermanshah Province of Iran. Sampling was based on recruitment of subjects according to inclusion and exclusion criteria. Patients with confirmed Parkinson disease who were referred to clinics of Kermanshah University of Medical Sciences participated in this study. Depression was evaluated with Beck Depression Inventory-II (BDI-II). Clinical characteristics of PD, including tremor, rigidity, impaired posture, loss of autonomic movement, changes in speech and handwriting, masked face, and hyposmia were indexed. Anhedonia was assessed with Farsi version of Snaith-Hamilton Pleasure Scale. Data were collected between April 2010 and March 2014. RESULTS: A total of 350 patients (52.9% men and 47.1% women) participated in this investigation. Female gender (36.5% in women vs. 13.0% in men, P < 0.0001), impaired posture (27.2% in affected individuals vs. 18.8%, P = 0.002), masked face (39.0% vs. 5.2%, P < 0.0001), and hyposmia (48.7% vs. 21.0%, P = 0.001) were associated with higher susceptibility to profound depression. Lower scores of all domains of Farsi version of Snaith-Hamilton Pleasure Scale (including interest/pastimes, social interaction, sensory experience, and food/drink) were related to more severe depression (P < 0.0001 for all subscales). Severe and profound depression was found in 44% of the participants. CONCLUSIONS: This study estimated that the prevalence of major depression among Iranian individuals with PD living in Kermanshah as 44%. Major determinants of depression were female gender, rigidity, impaired posture, masked face, hyposmia, and anhedonia.

Comparison of the genetic convergence between mycobacterium strains by three RFLP-based methods in central province of Iran.

OBJECTIVES: The utilization of molecular techniques in the epidemiology of tuberculosis have provided an opportunity for using effective markers to trace the transmission of the disease. The purpose of this study was to compare the genetic patterns of Mycobacterium tuberculosis by three methods of RFLP technique. MATERIALS AND METHODS: In a cross-sectional and prospective study, 95 strains of M. tuberculosis isolates were selected for DNA fingerprinting. Extraction of DNA from Mycobacterium strains and DNA fingerprinting with IS-6110, PGRS and DR probe were performed by standard protocols. RESULTS: Overall, the diversity of RFLP among 95 tuberculosis patients were 48, 50 and 45 on the basis of IS6110, PGRS and DR patterns, respectively. Twenty of these patterns (21.1%) with IS6110-RFLP, twenty-two (23.2%) with PGRS-RFLP and seventeen (17.9%) with DR-RFLP occurred with unique RFLP patterns, whereas the remaining 28 patterns were communal. The risk factors of clustering among tuberculosis patients were age < 45 years, new cases, degree of sputum smear ≥ 2+, and close contact. CONCLUSION: Our study demonstrated that IS6110-RFLP, PGRS-RFLP and DR-RFLP genotyping could roughly identify similar proportions of clustered (secondary) cases as well as the same risk factors for clustering.

Drug resistance pattern and associated risk factors of tuberculosis patients in the central province of Iran.

BACKGROUND: One of the fundamental issues of infectious disease treatment is drug resistance. The aim of the present study was to investigate the first-line anti-tuberculosis drug resistance rates and determine the risk factors related to multidrug resistant mycobacterium tuberculosis. METHODS: From March 2011 to September 2012, mycobacterial strains were collected from one hundred fifteen diagnosed smear positive patients in the central province of Iran and tested for drug susceptible against ethambutol, rifampicin, isoniazid and streptomycin and the risk factors influencing the development of drug resistance were determined. RESULTS: The mean age of patients was 52.23±19.75 years. The rate of multi-drug resistant tuberculosis (MDR-TB) was 7.8%. Our study revealed that there were significant associations between prior treatment, age < 45 years, positive smear result at the end of the second month and positive smear result at the end of the third month. However, there was no association found between gender, inhabitant, nationality, close contact with TB patient, HIV infection and size of mantoux test. CONCLUSION: The results show that about 8% of TB cases in Arak are MDR TB. The age under 45 years, previous TB treatment and positive smear at the end of the second and third months of treatment were the main factors in the development of MDR-TB.