Microvascular Sex- and Age- Dependent Phosphodiesterase Expression.

Objective: The cyclic nucleotide second messengers, cAMP and cGMP, are pivotal regulators of vascular functions; their cellular levels are tightly controlled by the cyclic nucleotide hydrolases, phosphodiesterases (PDE). Biologic sex and age are recognized as independent factors impacting the mechanisms mediating both vascular health and dysfunction. This study focused on microvessels isolated from male and female rats before (juvenile) and after (adult) sexual maturity under resting conditions. We tested the hypothesis that sexual dimorphism in microvascular PDE expression would be absent in juvenile rats, but would manifest in adult rats. Methods: Abdominal skeletal muscle arterioles and venules were isolated from age-matched juvenile and adult male and female rats under resting conditions. Transcripts of five PDE families (1-5) associated with coronary and vascular function with a total of ten genes were measured using TaqMan real-time RT-PCR and protein expression of microvessel PDE4 was assessed using immunoblotting and immunofluorescence. Results: Overall expression levels of PDE5A were highest while PDE3 levels were lowest among the five PDE families (p < 0.05) regardless of age or sex. Contrary to our hypothesis, in juveniles, sexual dimorphism in PDE expression was observed in three genes: arterioles (PDE1A, female > male) and venules (PDE1B and 3A, male > female). In adults, gene expression levels in males were higher than females for five genes in arterioles (PDE1C, 3A, 3B, 4B, 5A) and three genes (PDE3A, 3B, and 5A) in venules. Furthermore, age-related differences were observed in PDE1-5 (in males, adult > juvenile for most genes in arterioles; in females, adult > juvenile for arteriolar PDE3A; juvenile gene expression > adult for two genes in arterioles and three genes in venules). Immunoblotting and immunofluorescence analysis revealed protein expression of microvessel PDE4. Conclusion: This study revealed sexual dimorphism in both juvenile and adult rats, which is inconsistent with our hypothesis. The sex- and age-dependent differences in PDE expression implicate different modulations of cAMP and cGMP pathways for microvessels in health. The implication of these sex- and age-dependent differences, as well as the duration and microdomain of PDE1-5 activities in skeletal muscle microvessels, in both health and disease, require further investigation.

Chronic pulmonary mucormycosis: an emerging fungal infection in diabetes mellitus.

Mucormycosis commonly affects immunocompromised individuals with defects in neutrophil function or count. Diabetes mellitus is an important risk factor due to impair innate and acquired immunity for mucormycosis, with rhino-orbital-cerebral involvement as a common presentation. Pulmonary mucormycosis (PM) although a rare presentation in diabetic patients but is associated with high mortality and morbidity. An early diagnosis of PM is difficult, due to rarity of the disease and clinical and radiological features resembling tuberculosis (TB) which is common in Pakistan. Here we present three cases of chronic PM in patients with diabetes and with no other apparent risk factors.

Massive pulmonary embolism presenting as seizures.

Pulmonary embolism can present in various ways, though seizure activity has been rarely reported. We report a 38 years old male who had met a road traffic accident, underwent surgery, presented a month later with seizures, chest pain, shortness of breath and low blood pressure. Massive pulmonary embolism was diagnosed on CTPA, with classical features on ECG and echocardiogram and the patient was successfully managed with thrombolysis. Massive pulmonary embolism (MPE) should be kept in mind in patients who present with seizures, chest pain and haemodynamic instability.

Advancements in all-ceramics for dental restorations and their effect on the wear of opposing dentition.

Tooth wear is a process that is usually a result of tooth to tooth and/or tooth and restoration contact. The process of wear essentially becomes accelerated by the introduction of restorations inside the oral cavity, especially in case of opposing ceramic restorations. The newest materials have vastly contributed toward the interest in esthetic dental restorations and have been extensively studied in laboratories. However, despite the recent technological advancements, there has not been a valid in vivo method of evaluation involving clinical wear caused due to ceramics upon restored teeth and natural dentition. The aim of this paper is to review the latest advancements in all-ceramic materials, and their effect on the wear of opposing dentition. The descriptive review has been written after a thorough MEDLINE/PubMed search by the authors. It is imperative that clinicians are aware of recent advancements and that they should always consider the type of ceramic restorative materials used to maintain a stable occlusal relation. The ceramic restorations should be adequately finished and polished after the chair-side adjustment process of occlusal surfaces.

Clinical course and outcome of acute severe asthma (status asthmaticus) in adults.

OBJECTIVE: To evaluate the clinical course and outcomes in patients with acute severe asthma in a tertiary care setting. METHODS: The retrospective cross-sectional study was conducted at the Aga Khan University Hospital, Karachi, and comprised data of patients of age 16 and above who were admitted with a diagnosis of acute severe asthma from January 2000 to December 2013. These patients had undergone clinical evaluation to assess the severity of illness as well as the complications and eventual outcomes. SPSS 16 was used for statistical analysis. RESULTS: Of the 50 patients in the study, 41 (82%) were females. The overall mean age was 53.1±20.3 years. Ventilator support was required by 37(74%) patients. Presence of acidaemia was associated with the need for invasive ventilation (p<0.033) which in turn was associated with increased hospital stay (p<0.043). Complications were observed in 37(74%) patients, the most common being respiratory failure in 35(70%) and arrhythmias in 8(16%). Use of both non-invasive and invasive ventilation was found to be significantly associated with development of complications (p<0.001 and p<0.009). A total of 4(8%) patients died. Presence of acidaemia was found to be significantly associated with mortality (p<0.032). CONCLUSION: Overt acidaemia at initial presentation in patients with acute severe asthma was significantly associated with higher rates of invasive ventilation leading to increased hospital stay, complications and higher mortality rate.