Chagas disease reactivation in rheumatologic patients: association with immunosuppressive therapy and humoral response

Clinical Rheumatology - Evidence for Chagas disease reactivation (CDR) in rheumatologic patients under rheumatologic treatments (RTs) is scarce. To screen and follow-up patients with rheumatic...     

Hepatitis C: risk factors

Risk factors associated to at least 50% of hepatitis C cases are blood transfusion and injection-drug use. Less important factors are high-risk sexual behavior, job appointment in a healthcare setting and hemodialysis. Intra-familial and perinatal transmission are minor contributors to the overall prevalence of infection. The role of tattooing, acupuncture and piercing in hepatitis C transmission is controversial. There is still an important number of cases in whom no risk factor can be identified.     

Cellular basis for progesterone neuroprotection in the injured spinal cord

Progesterone (PROG) exerts beneficial and neuroprotective effects in the injured central and peripheral nervous system. In the present work, we examine PROG effects on three measures of neuronal function under negative regulation (choline acetyltransferase [ChAT] and Na,K-ATPase) or stimulated (growth-associated protein [GAP-43]) after acute spinal cord transection injury in rats. As expected, spinal cord injury reduced ChAT immunostaining intensity of ventral horn neurons. A 3-day course of intensive PROG treatment of transected rats restored ChAT immunoreactivity, as assessed by frequency histograms that recorded shifts from predominantly light neuronal staining to medium, dark or intense staining typical of control rats. Transection also reduced the expression of the mRNA for the alpha3 catalytic and beta1 regulatory subunits of neuronal Na,K-ATPase, whereas PROG treatment restored both subunit mRNA to normal levels. Additionally, the upregulation observed for GAP-43 mRNA in ventral horn neurons in spinal cord-transected rats, was further enhanced by PROG administration. In no case did PROG modify ChAT immunoreactivity, Na,K-ATPase subunit mRNA or GAP-43 mRNA in control, sham-operated rats. Further, the PROG-mediated effects on these three markers were observed in large, presumably Lamina IX motoneurons, as well as in smaller neurons measuring approximately <500 micro2. Overall, the stimulatory effects of PROG on ChAT appears to replenish acetylcholine, with its stimulatory effects on Na,K-ATPase seems capable of restoring membrane potential, ion transport and nutrient uptake. PROG effects on GAP-43 also appear to accelerate reparative responses to injury. As the cellular basis for PROG neuroprotection becomes better understood it may prove of therapeutic benefit to spinal cord injury patients.     

Drugs in clinical development for chronic obstructive pulmonary disease

Many drugs may be potentially useful in the treatment of chronic obstructive pulmonary disease (COPD), but relatively few become available for human use due to lack of safety, lack of efficacy, or both. This is an inherent risk in the drug development process, which coupled with the limited understanding of the molecular pathogenesis of COPD, has produced a trend toward improving existing compounds rather than to develop new compounds. This review focuses on improved existing compounds and newly discovered compounds that are in clinical trials, but not yet marketed. The improved existing compounds include: isomers of the long-acting bronchodilators, once-daily beta2-adrenoceptor agonists, anticholinergics and corticosteroids. The pool of novel compounds is in constant fluctuation and comprises anti-inflammatory drugs, antioxidants, leukotriene modifiers and a number of compounds aimed at treating different aspects of COPD such as pulmonary hypertension and hypophosphatemia.     

Parasite biodiversity in Rattus spp caught in wet markets

Rattus spp trapped in wet markets in Quiapo, Manila and Balayan, Batangas had ectoparasites, Echinolaelaps echidnius (mite), and Polyplax spinulosa (louse). The endoparasites identified were Hymenolepis diminuta; the acanthocephalan Moniliformis moniliformis; Taenia taeniaeformis strobilocercus larvae and Capillaria hepatica in liver; Trichosomoides crassicauda of the urinary bladder; Sarcocystis sp of muscle tissue; and two different species of stronglyloid-looking intestinal nematodes. Rats had 100% infection with C. hepatica and T. taeniaeformis, exhibiting high parasitemia. The co-existence of rats with diverse parasitic species is reflective of the host's capability to support parasites' behavioral, physiological, and developmental needs. Despite heavy infection with intestinal parasites, and marked hepatic tissue damage owing to severe capillariasis and strobilocercus larval infection, all rats appeared healthy and agile, suggestive of a well-established rat host-parasite relationship. In view of the diversity and zoonotic nature of rat parasites, and the impoverished conditions prevailing in communities where Rattus spp survive and proliferate, they can readily facilitate parasite transmission to humans and other susceptible animal hosts.     

Cell culture protection and<Emphasis Type="Italic">in vivo</Emphasis> neuroprotective capacity of flavonoids

Flavonoids are an important group of recognized antioxidants ubiquitous in fruits, vegetables and herbs. There are epidemiological evidences for the stroke-protecting capacity of flavonoids and while the neuroprotective power of complex extracts rich in flavonoids like those of Ginkgo biloba, green tea or lyophilized red wine have been demonstrated in several studies, neuroprotection by individual flavonoids has been poorly studiedin vivo. The neuroprotective capacity of individual flavonoids was studied in PC12 cells in culture and in a model of permanent focal ischemia (permanent Middle Cerebral Artery Occlusion — pMCAO). In thein vivo experiments, flavonoids were administered in lecithin preparations to facilitate the crossing of the blood brain barrier.     

Cholinergic Involvement in Alzheimer’s Disease. A Link with NGF Maturation and Degradation

Basal forebrain cholinergic neurons are highly dependent on nerve growth factor (NGF) supply for the maintenance of their cholinergic phenotype as well as their cholinergic synaptic integrity. The precursor form of NGF, proNGF, abounds in the CNS and is highly elevated in Alzheimer’s disease. In order to obtain a deeper understanding of the NGF biology in the CNS, we have performed a series of ex vivo and in vivo investigations to elucidate the mechanisms of release, maturation and degradation of this neurotrophin. In this short review, we describe this NGF metabolic pathway, its significance for the maintenance of basal cholinergic neurons, and its dysregulation in Alzheimer’s disease. We are proposing that the conversion of proNGF to mature NGF occurs in the extracellular space by the coordinated action of zymogens, convertases, and endogenous regulators, which are released in the extracellular space in an activity-dependent fashion. We further discuss our findings of a diminished conversion of the NGF precursor molecule to its mature form in Alzheimer’s disease as well as an augmented degradation of mature NGF. These combined effects on NGF metabolism would explain the well-known cholinergic atrophy found in Alzheimer’s disease and would offer new therapeutic opportunities aimed at correcting the NGF dysmetabolism along with Aβ-induced inflammatory responses.