Antituberculous immunity: new solutions to an old problem

Tuberculosis continues to be a serious public health problem worldwide. In Europe and the United States, it is now primarily a disease of the elderly; the alcoholic; the drug abuser; Central American, African, and Asian immigrants; and patients with AIDS. New and improved antituberculous vaccines are urgently needed, as both prophylactic and therapeutic agents. Recent advances in molecular biology, genetic engineering, and hybridoma technology make it possible to identify and clone the genes thought to be responsible for the production of the protective antigens (or epitopes) of Mycobacterium tuberculosis. These antigens are produced by the pathogen as it multiplies within the lymphoreticular organs of the infected host. The "protective" genes can be transferred to suitable expression vectors by means of shuttle phasmids, making possible the development of specifically tailored vaccines capable of protecting infants and young adults more effectively against pulmonary tuberculosis and immunocompromised individuals against the disseminated form of this disease.     

The TB pandemic: an old problem seeking new solutions

Tuberculosis (TB) continues to kill more than 2 million people globally each year. Annual TB case notification rates have risen up to fourfold since the mid-1980s, with the highest rate of 1000/100,000 around Cape Town, South Africa. There is an urgent need for novel diagnostic methods and preventive vaccines to control this epidemic. The rising incidence of TB has been attributed to HIV co-infection especially in developing countries. The threat of drug resistance arising from ineffective TB treatment programmes is looming and could potentially lead to loss of any gains made in controlling the disease globally.     

Loxoscelism: old obstacles, new directions

Loxosceles spiders have a worldwide distribution and are considered one of the most medically important groups of spiders. Envenomation (loxoscelism) can result in dermonecrosis and, less commonly, a systemic illness that can be fatal. The mechanism of venom action is multifactorial and incompletely understood. The characteristic dermonecrotic lesion results from the direct effects of the venom on the cellular and basal membrane components, as well as the extracellular matrix. The initial interaction between the venom and tissues causes complement activation, migration of polymorphic neutrophils, liberation of proteolytic enzymes, cytokine and chemokine release, platelet aggregation, and blood flow alterations that result in edema and ischemia, with development of necrosis. There is no definitive treatment for loxoscelism. However, animal model studies suggest the potential value of specific antivenom to decrease lesion size and limit systemic illness even when such administration is delayed.     

Bromocriptine: old drug, new formulation and new indication

Bromocriptine is an ergot alkaloid dopamine D₂ receptor agonist that has been used extensively in the past to treat hyperprolactinaemia, galactorrhoea and Parkinsonism. It is known that hypothalamic hypodopaminergic states and disturbed circadian rhythm are associated with the development of insulin resistance, obesity and diabetes in animals and humans. When administered in the early morning at the start of the light phase, a new quick release (QR) formulation of bromocriptine appears to act centrally to reset circadian rhythms of hypothalamic dopamine and serotonin and improve insulin resistance and other metabolic abnormalities. Phase II and III clinical studies show that QR‐bromocriptine lowers glycated haemoglobin by 0.6–1.2% (7–13 mmol/mol) either as monotherapy or in combination with other antidiabetes medications. Apart from nausea, the drug is well tolerated. The doses used to treat diabetes (up to 4.8 mg daily) are much lower than those used to treat Parkinson's disease and have not been associated with retroperitoneal fibrosis or heart valve abnormalities. QR‐bromocriptine (Cycloset?) has recently been approved in the USA for the treatment of type 2 diabetes mellitus (T2DM). Thus, a QR formulation of bromocriptine timed for peak delivery in the early morning may provide a novel neurally mediated approach to the control of hyperglycaemia in T2DM.     

Emerging applications for transseptal left heart catheterization old techniques for new procedures

Transseptal (TS) catheterization was introduced in 1959 as a strategy to directly measure left atrial (LA) pressure. Despite acceptable feasibility and safety, TS catheterization has been replaced by indirect measurements of LA pressure using the Swan-Ganz catheter. Today, TS puncture is rarely performed for diagnostic purposes but continues to be performed for procedures such as balloon mitral valvuloplasty, antegrade balloon aortic valvuloplasty, and ablation of arrhythmias in the LA. Thus, the "art" of TS puncture has been lost, except in centers that perform these procedures with regularity. Recently, there has been a renewed interest in the TS technique because of emerging therapeutic procedures for structural heart disease and atrial fibrillation ablation. Invasive cardiologists will have to refamiliarize themselves with the TS technique, newer TS devices, and advanced ultrasound imaging for guidance of the procedure.     

A-HeFT: old dog, new endothelial tricks

In conclusion, reduced nitric oxide bioactivity contributes to cardiac and vascular remodeling. Nitricoxide-enhancing therapy can slow cardiac andvascular remodeling. African-Americans with heart failure exhibit nitric oxide deficiency and a dramatic benefit from nitric-oxide-enhancing therapy. The potential benefit of this therapy in other groups with heart failure and in other vascular remodeling disease processes requires further study.     

Age-related bone loss: old bone, new facts

The human skeleton serves several functions for the body: support, locomotion, protection of vital organs, and housing of bone marrow. Bone remodeling is the result of the interactions of multiple elements, including osteoblasts, osteoclasts, hormones, growth factors, and cytokines, the end result being the maintenance of the bone architecture and to maintain systemic calcium homeostasis. In early life, a careful balance exists between bone formation by osteoblasts and bone resorption by osteoclasts. With aging, the process of coupled bone formation is affected by the reduction of osteoblast differentiation, activity, and life span which is further potentiated in the perimenopausal years with hormone deprivation and increased osteoclast activity. Age-related bone loss is thus not only a consequence of hormone deprivation, but also the result of changes in bone formation and cell-cell interactions with a unique pathophysiology. In this review, we describe the cellular and metabolic changes associated with aging bone and present recent evidence regarding cell differentiation within the bone marrow. We also consider the mechanism of programmed cell death, apoptosis, as being an important determinant of aging in bone as well as describe possible future interventions to prolong the life span of osteoblasts.