Peritoneal tuberculosis in Qatar: a five-year hospital-based study from 2005 to 2009

There is limited information about peritoneal tuberculosis in Qatar. This retrospective study aimed to review our experience with peritoneal tuberculosis in patients admitted to Hamad general hospital over a period of 5 years, from 2005 to 2009, with emphasis on presentation, investigation, diagnosis and therapeutic outcome. Fifty-four patients with peritoneal tuberculosis identified during the study period were included. The mean age of them was 31.85 years and 96.3% (52/54) of them were non-Qataris with male predominance. The main symptoms and signs at the time of presentation were abdominal pain and ascites respectively. Underlying diseases were described in 24% (13/54) and history of contact with tuberculous cases was present in 31.5% (17/54) of patients. Tuberculin test was positive in 66.7% (36/54). The ascitic fluid smear showed acid fast bacilli in 2% (1/53), and culture was positive in 39.6% (21/53) of cases. Laparoscopically obtained peritoneal biopsy showed caseating granulomas in 93% (40/43) and mycobacteria were identified by acid fast staining and culture in 58.5% (24/41) and 98% (40/41) of the tested specimens respectively. Most of the patients (84%; 37/44) who had completed their therapy in Qatar improved with antituberculosis therapy, and only one patient died. In conclusion, the clinical features and the imaging findings of the disease were non-specific. A high index of suspicion is essential for early diagnosis. Culture of ascitic fluid delayed the diagnosis in clinically suspected cases, whereas laparoscopically guided peritoneal biopsy provided rapid and correct diagnosis. A Six-month course with antituberculous therapy was effective and improved the outcome.     

Protective effects of oral arabic gum administration on gentamicin-induced nephrotoxicity in rats.

Arabic gum (AG) is a complex polysaccharide used as suspending agent. It has been widely used by eastern folk medicine practitioners as a restorative agent and is thought to be an excellent curative for renal failure patients. We therefore tested these folkloric claims using a rat model of gentamicin (GM)-induced nephrotoxicity. AG (7.5g 100ml(-1), in drinking water) was administered orally for 8 days concurrently with GM (80mgkg(-1) per day, i.p.). Estimation of urine volume, serum creatinine and urea concentrations, kidney tissue malondialdehyde (MDA) contents and glutathione (GSH) were carried out after the last dose of GM. Kidneys were also examined for histological changes. GM caused a marked nephrotoxicity as evidenced by significant increases in urine volume (295%), serum creatinine (318%) and urea (258%) and a significant decrease in creatinine clearance (Ccr) (26%). Treatment with AG protected the rats from GM-induced nephrotoxicity as evident by normalisation of these parameters. In addition there was about 187% increase in kidney tissue MDA contents above the control with GM treatment. AG totally prevented the GM-induced rise in kidney tissue contents of MDA. Kidney histology of the tissue from GM-treated rats showed necrosis and desquamation of tubular epithelial cells in renal cortex as well as interstitial nephritis. Whereas it was very much comparable to control when AG was co-administered with GM. In conclusion, AG protected the rats from GM-induced nephrotoxicity, possibly, at least in part through inhibition of the production of oxygen free radicals that cause lipid peroxidation.     

Neuroprotective effects of thymoquinone against transient forebrain ischemia in the rat hippocampus

Increasing evidence demonstrates that oxidative stress plays an important role in brain injury in experimental models of brain ischemia. Thymoquinone, the main constituents of the volatile oil from Negella sativa seeds, is reported to possess strong antioxidant properties. Hence, the present study was undertaken to evaluate the neuroprotective effect of thymoquinone against transient forebrain ischemia-induced neuronal damage in the rat hippocampus. Rats were divided randomly into five groups: control, sham, ischemia, thymoquinone and ischemia+thymoquinone. Transient forebrain ischemia was induced with bilateral occlusion of both common carotid arteries for 10 min followed by 7 days of reperfusion. Thymoquinone was administered (5 mg/kg/day p.o.) 5 days before ischemia and continued during the reperfusion time. Animals were sacrificed, and brain tissues were isolated for histopathological examination. Hippocampal tissues were also used for determination of malondialdehyde levels, an end product of lipid peroxidation; glutathione (GSH) levels, a key antioxidant and the activities of the antioxidant enzymes catalase and superoxide dismutase (SOD). Thymoquinone and its metabolite thymohydroquinone were tested as inhibitors of the in vitro non-enzymatic lipid peroxidation induced by iron-ascorbate in the hippocampal homogenate. Forebrain ischemia-reperfusion neural injury in rats was demonstrated by histopathological observation, which revealed significant neural cell death in the hippocampus CA1 area 7 days post-ischemia (77% cell loss). Additionally, forebrain ischemia-reperfusion oxidative injury in rats was demonstrated by a significant increase in malondialdehyde and a significant decrease in GSH contents, catalase and SOD activities in the hippocampal tissue compared to the control or sham-operated groups. Pretreatment of thymoquinone attenuated forebrain ischemia-induced neuronal damage manifested by significantly decreasing the number of dead hippocampal neuronal cells (24% in thymoquinone-treated versus 77% for ischemia, P<0.001), which confirm the protective role of thymoquinone in ischemia-reperfusion injury. Also, pretreatment of ischemic rats with thymoquinone decreased the elevated levels of malondialdehyde and increased GSH contents, catalase and SOD activities to normal levels. Thymoquinone and thymohydroquinone inhibited the in vitro non-enzymatic lipid peroxidation in hippocampal homogenate induced by iron-ascorbate. The IC50 for thymoquinone and thymohydroquinone were found to be 12 and 3 microM respectively. This suggests that the protection of thymoquinone and its metabolite involve increased resistance to oxidative stress. In conclusion, thymoquinone is effective in protecting rats against transient forebrain ischemia-induced damage in the rat hippocampus. This spectacular protection makes thymoquinone a promising agent in pathologies implicating neurodegenaration such as cerebral ischemia.     

Studies on the reproductive, cytological and biochemical toxicity of Ginkgo Biloba in Swiss albino mice

Ginkgo biloba (an herbal product), used as a folkloric medicine in the treatment of dementia, was evaluated for its effects on reproductive, cytological and biochemical toxicity in male Swiss albino mice. The mice were treated with different doses (25, 50 and 100mg/kg/day) of the aqueous suspension of Ginkgo biloba for 90 days by oral gavage. The following parameters were evaluated: (1) reproductive organ weight; (2) motility and content of sperms; (3) spermatozoa morphology; (4) cytology of the testes chromosomes; (5) study on reproduction; (6) biochemical study on proteins, nucleic acids, malondialdehyde (MDA) and nonprotein sulfhydryl (NP-SH). The treatment caused significant changes in the weight of caudae epididymis, prostate, chromosomal aberrations, rate of pregnancy and pre-implantation loss. However, the percent motility, sperm count and morphology of spermatozoa were not affected. Our study on biochemical parameters showed depletion of nucleic acids, NP-SH and increase of MDA, which elucidated the role of free radical species in the induced changes in testis chromosomes and the reproductive function. The exact mechanism is not known, however, the activation of GABA, glycine and glutamate under the influence of Ginkgo biloba and its constituents might have generated free radicals and depleted cellular glutathione by calcium influx and membrane depolarization. The observed toxicity is attributed to the toxic constituents (ginkgolic acids, biflavones, cardanols, cardols, bilobalides and quercetin) of Ginkgo biloba. Our results warrant careful use of Ginkgo biloba as a remedy for impotence and/or erectile dysfunction.     

L-Carnitine halts apoptosis and myelosuppression induced by carboplatin in rat bone marrow cell cultures (BMC)

Carboplatin (CP), a second generation platinum compound, is effective against various types of cancers, producing less nephrotoxicity and ototoxicity but more myelotoxicity than cisplatinum. CP-myelosuppression is the rate-limiting step of its clinical use. Prevention of CP-myelosuppression is a major target in the field of chemotherapy. Therefore, the present study investigates the use of L-carnitine (LCR)—an antioxidant, cardioprotective, neuroprotective, and immunostimulant nontoxic natural compound—to protect against CP-induced myelosuppression. The viability of BMC was studied using a trypan blue exclusion technique following incubation with CP and/or LCR as a function of time and concentration. Apoptosis was tested for by detecting the amount of DNA fragmentation and the visualization of DNA ladders upon gel electrophoresis. Bone marrow progenitor cell function was examined by colony forming unit assay. Cellular contents of glutathione (GSH) and malondialdehyde (MDA) were also estimated. Results revealed that LC50 of CP is 4.7 mM and the highest safe concentration of LCR is 5 mM. Co-exposure of LCR+CP rescued BMC viability by 37% compared to the CP-treated cultures. The LCR halts CP-induced apoptosis and it significantly improves the function of the bone marrow progenitors by increasing the number of colony-forming units as a response to granulocyte/macrophage colony stimulating factors. Finally, LCR restores CP-induced GSH depletion and prevents MDA elevation in BMC. In summary, the results suggest that LCR is able to protect against CP-induced myelosuppression, which suggests its use as an adjuvant therapy. This finding merits further investigation into the mechanism(s) of such protection as well as its interaction with CP antitumor activity.     

Depressed patients’ preferences for education about medications by pharmacists in Kuwait

Objective

To assess patients’ opinion toward receiving written or specialized verbal pharmacists’ interventions and to determine the effect of these interventions on patients’ medication knowledge.

Methods

150 newly diagnosed patients with unipolar depression and initiated with a single antidepressant were randomized into 3 groups: control, leaflet and counselling, and interviewed at initiation and after 6–8 weeks of treatment at the outpatient department of the Psychiatric Hospital in Kuwait.

Results

50% of respondents asserted that clinicians did not give them sufficient information while 90% favoured the idea of receiving further information about therapy. Forty seven percent of participants failed to return for the second follow-up appointment. The drop-out rate was 66% in the control, 42% in the Leaflet and only 34% in the counselling groups (P = 0.004). A broad support for receiving leaflets and drug counselling (97%) was found among attendees. Moreover, 94% of the counselling and 79% of the leaflets group affirmed that they received adequate information compared to 47% of the control (P = 0.001). Counselling was found to be significantly associated with a much higher recall of medicine name (OR = 9.6, P = 0.01), how to manage missed doses (OR = 8.9, P = 0.007), and correct use of medication (OR = 31.3, P < 0.001). Leaflet use was less strongly associated than counselling and was statistically significant for recall regarding correct use of medication (OR = 8.4, P = 0.009).

Conclusion

Pharmacists in a psychiatric institution can play an important role in satisfying patient demands for specialized information about their medications. Patients with depression appear very eager to receive additional drug information with modest difference between the written and the verbal counselling interventions. Patients looked at the two interventions in a very positive manner and no difference was observed between patients in the leaflets and in the counselling group with regards to how helpful, sufficient, supportive and reassuring was the educational material. However, both interventions were more informative than the control in conveying elemental drug information to patients.

Practice Implications

In contrast with the lack of enthusiasm that some clinicians express, the affirmativeness that was expressed by patients towards receiving written or verbal specialized educational interventions by pharmacists may support the psychiatric hospital pharmacists’ stands in providing them for all patients which may aid in improving patients compliance and probably treatment outcome.     

Optimized Rivastigmine Nanoparticles Coated with Eudragit for Intranasal Application to Brain Delivery: Evaluation and Nasal Ciliotoxicity Studies

Rivastigmine, a reversible cholinesterase inhibitor, is frequently indicated in the management of demented conditions associated with Alzheimer disease. The major hurdle of delivering this drug through the oral route is its poor bioavailability, which prompted the development of novel delivery approaches for improved efficacy. Due to numerous beneficial properties associated with nanocarriers in the drug delivery system, rivastigmine nanoparticles were fabricated to be administer through the intranasal route. During the development of the nanoparticles, preliminary optimization of processing and formulation parameters was done by the design of an experimental approach. The drug–polymer ratio, stirrer speed, and crosslinking time were fixed as independent variables, to analyze the effect on the entrapment efficiency (% EE) and in vitro drug release of the drug. The formulation (D8) obtained from 2³ full factorial designs was further coated using Eudragit EPO to extend the release pattern of the entrapped drug. Furthermore, the 1:1 ratio of core to polymer depicted spherical particle size of ~175 nm, % EE of 64.83%, 97.59% cumulative drug release, and higher flux (40.39 ± 3.52 µg.h/cm²). Finally, the intranasal ciliotoxicity study on sheep nasal mucosa revealed that the exposure of developed nanoparticles was similar to the negative control group, while destruction of normal architecture was noticed in the positive control test group. Overall, from the in vitro results it could be summarized that the optimization of nanoparticles’ formulation of rivastigmine for intranasal application would be retained at the application site for a prolonged duration to release the entrapped drug without producing any local toxicity at the mucosal region.