Francisella tularensis: possible agent in bioterrorism.

Francisella tularensis, the causative agent of tularemia, is a highly infectious gram-negative coccobacillus. Due to its high infectivity it is of major concern to public health officials as a possible biological weapon. Although accidental exposure can occur through arthropod bites, handling infected animals, or breathing in aerosols, cases are usually isolated and contained. In the event of an intentional exposure such as in a bioterrorist attack, inhalation of aerosols can result in devastating consequences with much causality. Although a vaccine is available, sufficient quantities may not be readily accessible in an actual attack. Therefore, it is very important for both medical professionals and public health officials to be prepared to contain and control the situation should it actually occur.     

Chlamydial infections of the heart

Chlamydiae are common human pathogens, causing a broad spectrum of infectious diseases. Chlamydial infections involving the heart have been described in numerous previous reports. These organisms are documented to cause endocarditis, myocarditis and pericarditis. Furthermore,Chlamydia pneumoniae, the recently discovered respiratory pathogen, has also been implicated in coronary artery disease. For the first time the literature on involvement of the heart in chlamydial infections is reviewed. Information on the discovery ofChlamydia species is also included and the problem of the species determination ofChlamydia in interpretation of the older literature is mentioned.     

Innovative pulmonary targeting of terbutaline sulfate-laded novasomes for non-invasive tackling of asthma: statistical optimization and comparative in vitro/in vivo evaluation

Asthma represents a globally serious non-communicable ailment with significant public health outcomes for both pediatrics and adults triggering vast morbidity and fatality in critical cases. The β₂-adrenoceptor agonist, terbutaline sulfate (TBN), is harnessed as a bronchodilator for monitoring asthma noising symptoms. Nevertheless, the hepatic first-pass metabolism correlated with TBN oral administration mitigates its clinical performance. Likewise, the regimens of inhaled TBN dosage forms restrict its exploitation. Consequently, this work is concerned with the assimilation of TBN into a novel non-phospholipid nanovesicular paradigm termed novasomes (NVS) for direct and effective TBN pulmonary targeting. TBN-NVS were tailored based on the thin film hydration method and Box-Behnken design was applied to statistically optimize the formulation variables. Also, the aerodynamic pattern of the optimal TBN-NVS was explored via cascade impaction. Moreover, comparative pharmacokinetic studies were conducted using a rat model. TBN elicited encapsulation efficiency as high as 70%. The optimized TBN-NVS formulation disclosed an average nano-size of 223.89 nm, ζ potential of −31.17 mV and a sustained drug release up to 24 h. Additionally, it manifested snowballed in vitro lung deposition behavior in cascade impactor with a fine particle fraction of 86.44%. In vivo histopathological studies verified safety of intratracheally-administered TBN-NVS. The pharmacokinetic studies divulged 3.88-fold accentuation in TBN bioavailability from the optimum TBN-NVS versus the oral TBN solution. Concisely, the results proposed that NVS are an auspicious nanovector for TBN pulmonary delivery with integral curbing of the disease owing to target specificity.     

DHA-Enriched Fish Oil Ameliorates Deficits in Cognition Associated with Menopause and the APOE4 Genotype in Rodents

Female APOE4 carriers have a greater predisposition to developing Alzheimer’s disease (AD) compared to their male counterparts, which may partly be attributed to menopause. We previously reported that a combination of menopause and APOE4 led to an exacerbation of cognitive and neurological deficits, which were associated with reduced brain DHA and DHA:AA ratio. Here, we explored whether DHA-enriched fish oil (FO) supplementation mitigated the detrimental impact of these risk factors. Whilst DHA-enriched fish oil improved recognition memory (NOR) in APOE4 VCD (4-vinylcyclohexene diepoxide)-treated mice (p < 0.05), no change in spatial working memory (Y-maze) was observed. FO supplementation increased brain DHA and nervonic acid and the DHA:AA ratio. The response of key bioenergetic and blood–brain barrier related genes and proteins provided mechanistic insights into these behavioural findings, with increased BDNF protein concentration as well as mitigation of aberrant Erβ, Cldn1 and Glut-5 expression in APOE4 mice receiving fish oil supplementation (p < 0.05). In conclusion, supplementation with a physiologically relevant dose of DHA-enriched fish oil appears to offer protection against the detrimental effects of menopause, particularly in “at-risk” APOE4 female carriers.     

Thiosemicarbazide functionalized carbon quantum dots as a fluorescent probe for the determination of some oxicams: application to dosage forms and biological fluids

In this study, highly fluorescent water-soluble nitrogen and sulfur doped carbon quantum dots (N, S-CQDs) were synthesized via a one-step hydrothermal process utilizing citric acid as a carbon source and thiosemicarbazide as a sulfur and nitrogen source. The obtained N, S-CQDs exhibited an intense emission band at 415 nm (λ_ex = 345 nm). In the presence of either piroxicam, tenoxicam or lornoxicam, the emission band at 415 nm was significantly quenched which might be triggered due to destruction of the surface passivation layer of the N, S-CQDs. A linear correlation was found between the reduction in the fluorescence intensity of N, S-CQDs and the concentration of each drug in the ranges of 2.0–25.0 μM, 10.0–100.0 μM and 20.0–200.0 μM with correlation coefficients of more than 0.999 for all drugs. The detection limits were 0.49 μM, 1.58 μM and 4.63 μM for piroxicam, tenoxicam and lornoxicam, respectively. The effect of experimental parameters affecting the performance of the method was investigated and optimized. The developed sensor has the advantages of simplicity, time-saving, convenience and satisfactory selectivity for determination of the studied drugs in dosage forms with high % recoveries (98.86–101.69%). The method was extended for determination of piroxicam in spiked plasma with % recoveries ranging from 97.95–101.36%. The method was validated in accordance with International Council of Harmonization (ICH) standards, and the results obtained were compared statistically to those given by reported methods, indicating no significant differences in the level of accuracy and precision. The mechanism of the quenching process was studied and elucidated. The structure–activity relationship between the three drugs and the quenching efficiency was also studied and discussed.

Highly fluorescent nitrogen and sulfur doped carbon quantum dots were synthesized via hydrothermal process using citric acid and thiosemicarbazide. The dots had an emission band at 415 nm (λ_ex = 345 nm). The polarity of the studied drugs affects the method’s sensitivity.     

Leptospirosis among zebu cattle in farms in Kaduna State,Nigeria

ObjectiveTo assess the occurrence of Leptospira spp serovar Hardjo among Zebu cattle in some livestock producing areas of Kaduna State, Nigeria.MethodsSera samples were obtained from 164 Zebu breed of cattle above one year osf age in seven cattle farms were screened for antibodies to Leptospira spp. serovar Hardjo using Enzyme linked immunosorbent assay (ELISA).ResultsAntibodies to Leptospira spp. serovar Hardjo were detected in eighteen (10.98%) out of the 164 animals sampled. There was no significant difference (P>0.05) in seropositivity between the different age groups or between different Zebu breeds.ConclusionThe presence of Leptospirosis among the Zebu breeds of cattle may poses a threat to livestock production and has public health implication due to its zoonotic potential.     

Pharmacokinetics of cyclosporine in monkeys after oral and intramuscular administration: relation to efficacy in kidney allografting

In cynomolgus and rhesus monkeys, the dose-normalized exposure of cyclosporine administered orally as microemulsion preconcentrate (Neoral) was lower than that upon intramuscular administration. For oral administration, mean values ( ± SD) of C_max, 24-h area-under-the curve (AUC) and 24-h trough level, all normalized for a 1 mg/kg dose, were 20 ± 9 ng kg/mg ml, 210 ± 70 ng h kg/mg ml and 2.6 ± 0.9 ng kg/mg ml, respectively. For intramuscular administration, levels were about 5.5-fold, 9-fold and 22-fold higher. Based on pharmacokinetic data, the efficacy of oral cyclosporine treatment (without any other immunosuppressant) was evaluated in life-supporting cynomolgus monkey kidney allotransplantation. Rejection-free kidney allograft survival could be achieved using oral cyclosporine monotherapy with average 24-h trough concentrations above 100 ng/ml during maintenance treatment. Typically, daily oral doses of 100 mg/kg–150 mg/kg during the first two weeks post-transplantation, followed by daily 30 mg/kg–100 mg/kg dose levels during subsequent maintenance can result in long-term allograft survival, with 24-h average trough levels in individual animals during maintenance between 110 ng/ml and 700 ng/ml. Received: 1 October 1997 Revised: 20 April 2001 Accepted: 7 June 2001     

De novo malignant peripheral nerve sheath tumor of the breast: case report number one

Summary BACKGROUND: Sarcomas of the breast are rare, representing less than 1% of malignant breast tumours. Malignant peripheral nerve sheath tumour (MPNSTs) is the malignant counterpart to benign soft tissue tumours such as neurofibromas and schwannomas. It is the most common sarcoma arising in the setting of von Recklinghausen's disease. METHODS: We report a de novo malignant peripheral nerve sheath tumour of the breast in 18-year-old patient. To the best of our knowledge, this is the first reported case of sporadic MPNST occurring in the breast in the absence of neurofibromatosis. RESULTS: Immunohistochemical examination is essential to establish the diagnosis and helpful in excluding other lesions in the differential diagnosis. CONCLUSIONS: The surgeon should approach these tumours according to the established guidelines for soft tissue sarcoma surgery.      

Problem pulmonary pathogens: Pseudomonas aeruinosa

Pseudomonas aeruginosa is a common and highly lethal agent of nosocomial pneumonia, especially among patients receiving mechanical ventilation. It is widespread in the environment and commonly recovered from water in nature and in hospital settings. P. aeruginosa is endowed with a formidable array of virulence factors that facilitate attachment to host cells, tissue invasion, and systemic disease. It is intrinsically resistant to many commonly used antibiotics due to a complex variety of mechanisms that we will briefly review. Recent advances in the understanding of the molecular biology of this organism have shed considerable light on its ability to form biofilms, which facilitate adherence especially in cystic fibrosis patients, and confer resistance to clearance by host immune mechanisms and antimicrobial killing. Treatment studies have demonstrated a significant risk of emergence of resistance during therapy with a variety of agents. Several studies suggest that two drugs are better than one for therapy of serious infections, although dual therapy does not always prevent emergence of resistant strains.