Combined pain and depression status in rats was created by inducing experimental depressive syndrome (by subchronic injection of MPTP proneurotoxin) in animals with manifest and developing neurogenic pain syndrome induced by preliminary crossing of the sciatic nerve in the hind limb. The neurogenic pain syndrome augmented by some parameters the depressive symptoms and provoked manifestation of signs of depressive behavior in animals treated with saline.

Besides structural and functional deficits, central nervous system (CNS) damage causes another effect in the form of novel pathological integrations consisting of CNS primarily and secondarily changed structures. At the neuronal level, the integration presents as aggregation of hyperactive uncontrollable neurons, which produces enhanced uncontrolled impulse flow and acts as a generator of pathologically enhanced excitation, network type. At the system interrelation level, the integration is represented by a new pathodynamic organization including damaged CNS regions, which constitutes a pathological system (PS). The hyperactive CNS structure plays a role of a pathological determinant promoting PS formation may determine a type of PS activity. A clinical manifestation of PS activity is a corresponding neurological or psychopathological syndrome.

The active loading of liposomes with dopamine in response to an ammonium sulfate gradient was studied. This method can be regarded as a mean to more efficiently improve the liposomal dopamine/lipids ratio in comparison to conventional methods of liposome preparation. Trapping efficiency of dopamine into liposomes exhibiting a transmembrane ammonium sulfate gradient was shown to be dependent on liposome lipid composition, lipid concentration and temperature. Dopamine-containing liposomes with α-tocopherol in the lipid bilayer were shown to be stable at least for three weeks. It has been found that intraperitoneal (i.p.) administration of conventionally prepared dopamine-containing liposomes as well as liposomes with increased dopamine/lipid ratio may efficiently suppress the expression of parkinsonian symptoms in C57BL/6 mice with experimental parkinsonian syndrome. On the other hand, only through increasing of liposomal dopamine/lipid ratio the complete compensation of dopamine deficiency in the mice brain was achieved. The obtained data may be considered as biochemical evidence in favor of liposomes' ability to act as a carrier system for the delivery of dopamine into the brain.

Cardiothoracic surgeons and practitioners of cardiovascular medicine have a long history of humanitarian aid. Although this is worthwhile at multiple levels and occasionally described in some detail, few efforts have a proven algorithm with demonstrable outcomes that suggest effective educational methodology or clinical results approaching accepted standards in developed countries.Our report provides a stepwise approach to developing highly successful self-sustainable, replicable, and scalable humanitarian congenital cardiac surgical programs, and provides data to allow insight into the efficacy of our model.This program model has evolved over 25 years, during which it has been replicated several times and scaled throughout a vast and populous country. Since 1989, Russia has undergone considerable social, political, and economic changes. Our program model proved successful throughout this time despite dynamic social, political, and medical landscapes.The positive results of our program model indicate that these methodologies may be helpful to others attempting to address the worldwide shortage of cardiovascular care and particularly the complex interventions required in the management of congenital cardiovascular disease.

The effects of substance P (SP) fragments on pathological pain has been studied in rats with a spinal pain syndrome. The spinal pain syndrome was elicited by creating the generator of pathologically enhanced excitation in spinal lumbar dorsal horns. The generator was induced by applying penicillin, which caused disturbances in GABAergic inhibition. It has been shown that the N- and C-terminal fragments of SP have antagonistic modulating effects on pathological pain. The N-terminal fragment, SP1–4, enhances the spinal pain syndrome, while the C-terminal fragment, SP5–11, inhibits pain paroxysms. Microinjection of SP5–11 into dorsal raphe nucleus, the antinociceptive structure, produces pronounced and prolonged suppression of the spinal pain syndrome immediately after the injection and increases the neuronal activity in this nucleus. The analgesic effect of fragment SP5–11 established in this study suggests that this derivative of the whole SP molecule acts as an activator of the antinociceptive system.

Diuretics, when added to angiotensin-converting enzyme inhibitors (ACE inhibitors) treatment, can augment the response to ACE inhibitors, but may have adverse effects on renal function, which negatively affect prognosis. While in heart failure rats combined therapy initially improved cardiac function and prognosis, this benefit was completely lost at later stages. We now studied renal effects of adding hydrochlorothiazide to ACE inhibitor after myocardial infarction in rats. Rats were randomized to ACE inhibitor quinapril monotherapy or quinapril with add-on hydrochlorothiazide. Survival was monitored for 14 months. Plasma creatinine, measured at 4 months, was increased by 40% in quinapril with add-on hydrochlorothiazide compared to quinapril. Although overall 14-months mortality was similar in quinapril with add-on hydrochlorothiazide and quinapril, stratification based on plasma creatinine showed increased mortality in the tertile with highest plasma creatinine (P = 0.03, Log rank). With add-on hydrochlorotiazide, renal morphology displayed severe renal interstitial lesions; tubular dilatation and fibrosis. Interstitial myofibroblast transformation (α-smooth muscle actine staining) was increased at 8 and 14 months, and coincided with collagen deposition and interstitial inflammation (macrophage influx). In rats with quinapril monotherapy or untreated rats, renal structure was normal. Thus, adding hydrochlorotiazide to ACE inhibitor detrimentally affected not only renal function, but also renal structure in rats with myocardial infarction. Altered pharmacokinetics, resulting from a vicious circle of reduced renal function and increased circulating drug levels, may provide an explanation for the adverse renal effects and may exert unfavorable effects on long-term prognosis after myocardial infarction.

Methamphetamine has become one of the most widely used illicit substances in the world. We measured the prevalence and identified the correlates of methamphetamine use amongst current injection drug users (IDUs) in a China–Myanmar border region.A cross-sectional survey including interviews and serological testing was conducted in 2012. Chinese IDUs who had injected within the past six months and aged ≥18 years were recruited using respondent-driven sampling (RDS). Logistic regression indentified factors associated with current methamphetamine use.Among 370 IDUs recruited, prevalence of lifetime and current methamphetamine use was 84.2% and 75.2% respectively. Amongst 293 current users, 18.1% ever purchased methamphetamine from Myanmar while 8.9% ever used it there during the past 6 months. IDUs who had cross-border activities, including purchasing drugs (AOR: 1.20; 95% CI: 1.10, 1.31) and visiting family/friends, doing business or odd jobs in Myanmar (AOR: 1.13; 95% CI: 1.02, 1.24) were more likely to use methamphetamine in the past six months. Other factors independently associated with current methamphetamine use included being younger (aged ≤25 years, AOR: 1.24; 95% CI: 1.09, 1.41), being syphilis positive (AOR: 1.17; 95% CI: 1.03, 1.33), having used previously self-used needle/syringe (AOR: 1.20; 95% CI: 1.08, 1.34) and recently received prevention services (AOR: 1.15; 95% CI: 1.04, 1.28).Methamphetamine has become another major drug of use and poses the serious concern among injecting drug users living in the China/Myanmar border region. The bi-national cooperation is urgently needed to develop targeted effective intervention strategies.

Abstract The effects of neurotropin have been studied on a model of a neuropathic pain syndrome caused by sciatic nerve injury as well as on a model of the adjuvant arthritis pain syndrome caused by Freund's adjuvant injected into the plantar region of the lower limb. The experimental results suggest that neurotropin prevents the development of the neuropathic pain syndrome in many cases and relieves the pathological process in the already developed syndrome. However, neurotropin fails to prevent the development of adjuvant arthritis but markedly decreases its severity. Neurotropin normalized the thresholds of pain sensitivity upon thermal stimulation (`hot plate' method) which remain at a sufficiently high level also after cessation of neurotropin injections. The analgetic action of neurotropin is due to its suppressive effect on various links of the pathologic algic system.

YURASOV, W; KUCHERYANU, V G; NIKUSHKIN, E V; KRYZHANOVSKY, G N; SANDALOV, Y G; KAPLUN, A P Author Information

Laboratory of Nervous System Pathology, Institute of General Pathology and Pathophysiology, Academy of Medical Science, Moscow 125315, Russia

Human platelet monoamine oxidase (MAO) preferentially deaminated benzylamine and phenylethylamine, two substrates relatively specific for type B MAO, in comparison to 5-hydroxytryptamine, a substrate specific for type A MAO. In studies comparing human platelet and rat brain MAO specific activities, benzylamine and 5-hydroxytryptamine deamination by platelets was approximately 90 and 2 per cent, respectively, that of brain, while platelet deamination of dopamine, tryptamine and tyramine was 20 per cent or less than that of brain. Among sixteen drugs studied, platelet MAO activity was selectively inhibited by low concentrations of the MAO-B inhibitors, deprenyl and pargyline, and was relatively insensitive to the MAO-A inhibitors, clorgyline and Lilly 51641. These observations, in addition to the simple sigmoid inhibition curves obtained with increasing concentrations of either clorgyline or deprenyl, suggest that platelet MAO consists of essentially one distinguishable form of MAO which most closely resembles the MAO type B found in other tissues.