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PubMed2005

Tumor necrosis factor alpha and glutathione interplay in chronic heart failure.

The pro-inflammatory cytokine, tumor necrosis factor alpha (TNF alpha), in concert with neurohormones, contributes to chronic heart failure (CHF) progression. This implies that TNF a antagonism may constitute an important target for CHF therapy. However, clinical trials in CHF patients using compounds that trap TNF alpha, comprising infliximab, an antibody directed to TNF alpha, and etanercept, a soluble recombinant receptor of TNF alpha, gave disappointing results bringing back to light the dual, short-term beneficial and long-term harmful effect of TNF alpha. This review focuses on the dual, concentration- and time-related effects of TNF alpha, the yin and yang action of TNF alpha in cardiac ischemia/reperfusion and contraction. Importantly, the harmful effects of TNF a are related to glutathione deficiency, a common hallmark to several other chronic inflammatory diseases. Recently, in rat models of CHF, oral administration of the glutathione precursor, N-acetylcysteine (NAC), was shown to hinder pathways of TNF alpha harmful signalling and to rescue cardiac structure and function. These results suggest that glutathione deficiency in association with TNF alpha activation may play a role in the pathophysiology of CHF and that NAC may represent a potential therapy in CHF.

Acetylcysteine↗
PubMed2005

[Implementation of quality management in French hospitals: staff interplay and induced changes].

BACKGROUND: French hospitals have been encouraged to develop quality processes, in particular through the implementation of a mandatory accreditation. Our objectives were to study the models of quality management used in hospitals and to identify the induced changes in organisation and practices. METHODS: This multiple case study related to 9 acute care hospitals selected among the hospitals whose quality process were relatively old. The study was based on interviews related to 78 people including 26 administrative staff members, 33 physicians and 19 chief nurses. Implementation analysis and strategic analysis were applied. RESULTS: Accreditation played a major part in the institutionalisation of quality processes. Implementation appeared more complete in the small size and private statute hospitals compared to the large public statute hospitals. But the main factors accounting for implementation variability were the level of involvement of the executive directors and participation of doctors in the quality process' leadership. The most important changes were establishment of specific structures, appearance of new professions and elaboration of quality documentation. In the hospitals where the quality process was strongly implemented, there was a trend to the de-compartmentalization between the professions and between the structures and phenomena of employees'development and empowerment. CONCLUSION: Institutionalisation of quality management is recent and the level of implementation varies greatly among hospitals. Involving doctors remains a major challenge for the development of quality management so that the quality can lead changes in hospital.

Accreditation↗
PubMed2006

The hypothalamic-pituitary-adrenal and the hypothalamic- pituitary-gonadal axes interplay.

Vertebrates respond to stress with activation of the hypothalamic-pituitary-adrenal (HPA) axis, the adrenergic and the autonomic nervous systems. The principal central nervous system regulators of the HPA axis are corticotropin releasing hormone (CRH) and antidiuretic hormone (AVP). Apart from in the central nervous system, CRH has been found in the adrenal medulla, ovaries, myometrium, endometrium, placenta, testis and elsewhere. The activation of the HPA axis during stress affects all body systems. The reproductive axis is inhibited by the HPA axis for the sake of saving energy. The changes to the hypothalamic-pituitary-gonadal (HPG) axis during stress are species-specific, and depend on the type and duration of the stimulus. Several conditions may be associated with altered regulation of the HPA axis. Polycystic ovary syndrome, anorexia nervosa and pregnancy in the third trimester are all characterized by HPA axis activation. In contrast, during the postpartum period, HPA axis suppression is implicated in the "postpartum blues". The actions of CRH are also essential in fetal development and neonatal survival.

Adolescent↗
PubMedDate not supplied

Vanishing bile duct syndrome in a child with toxic epidermal necrolysis: an interplay of unbalanced immune regulatory mechanisms.

Vanishing bile duct syndrome (VBDS) is a rare disorder and requires a liver biopsy for a diagnosis. The condition has not been reported in children with toxic epidermal necrolysis (TEN). The etiology of VBDS in our patient with TEN is most likely from drug hypersensitivity. A high index of suspicion will prompt clinicians to start more specific investigations and treatments. The use of immunosuppressive agents, intravenous immunoglobulin and ursodeoxycholic acid has not been consistently successful in these patients. A new approach with biologic agents such as anti-tumor necrosis factor-alpha may be a promising therapy and reduce severe adverse outcomes.

Anti-Infective Agents↗
PubMed2006

Quiescent interplay between inducible nitric oxide synthase and tumor necrosis factor-alpha: influence on transplant graft vasculopathy in renal allograft dysfunction.

A healthy endothelium is essential for vascular homeostasis, and preservation of endothelial cell function is critical for maintaining transplant allograft function. Damage to the microvascular endothelial cells is now regarded as a characteristic feature of acute vascular rejection, an important predictor of graft loss. It is also linked with transplant vasculopathy, often associated with chronic allograft nephropathy. Large bursts of nitric oxide in infiltrating monocytes/macrophages modulated by inducible nitric oxide synthase are considered pivotal in driving this mechanism. Indeed, it has been shown recently that increased circulating levels of tumor necrosis factor-alpha in the rejecting kidneys are largely responsible for triggering inducible nitric oxide synthase expression. This in turn suggests that several structural and functional features of graft rejection could be mediated by tumor necrosis factor-alpha. Despite the large body of evidence that supports immunologic involvement, knowledge concerning the cellular and biochemical mechanisms for nephritic cell dysfunction and death is incomplete. The role of tumor necrosis factor-alpha in mediating pathophysiological activity of inducible nitric oxide synthase during transplant vasculopathy remains contentious. Here, we discuss the effect of inducible nitric oxide synthase and tumor necrosis factor-alpha interaction on progressive damage to glomerular and vascular structures during renal allograft rejection. Selective inhibition of inducible nitrous oxide synthase and tumor necrosis factor-alpha as a potential therapy for ameliorating endothelial dysfunction and transplant graft vasculopathy is also discussed.

Animals↗
PubMed1991

The interplay of ischemic and hypertensive pathophysiology on cardiac function.

Many patients with systemic hypertension also have concomitant angina pectoris. Hypertension is a risk factor for the development of coronary artery disease as well as an aggravating factor once symptomatic ischemic heart disease develops. It would be prudent to use one agent that reduced the elevated blood pressure and relieved anginal symptoms while providing no negative affects on hemodynamics or other cardiac risk factors. beta-Adrenergic blockers (traditional agents and newer compounds with ancillary properties) and calcium-entry blockers have been shown to be effective as monotherapies in patients with angina. They also have the ability to induce left ventricular hypertrophy regression. There is some evidence that some of these therapies may arrest the development of arteriosclerosis and may have an inhibitory effect on platelet aggregation. What remains controversial is the optimal amount of blood pressure reduction in patients with hypertension coexistent with angina, or whether one specific agent or drug class would have an overall advantage in reducing the risk of morbidity or mortality.

Adrenergic beta-Antagonists↗
PubMed1991

Interplay of microbe and major histocompatibility complex: a family study.

We describe a 24-year-old man who developed reactive arthritis (ReA) after a dysenteric illness caused by Salmonella hadar. Serologic tests suggested recent exposure of family members to Salmonella. All members of the family were HLA-B27 positive, but no other family member developed acute ReA, although 2 of them had clinical evidence of previously existing B27 associated arthritis.

Adult↗
PubMed1990

[Making a surgical decision: interplay between experience and clinical study].

Although the final, individual decision making in patients always has to be in the hand of the doctor, it has hitherto been much less a matter of scientific analysis than formal decision making on the basis of clinical trials. To change this, several types of individual decision making were characterized, four in the field of intuition (very fast logical decisions, consciously and unconsciously heuristic decisions using special instruments, the deep remainder of intuition which can and should not be the subject of scientific analysis) and discursive (purely logical) decision making as a fifth type. The prospective think-aloud technique including an hierarchical heuristic decision tree was presented as a method for scientific analysis of individual decision making which is open to repetition and criticism. The place of various types of formal trials in this process was defined. Via a posit and the heuristic instrument of representativeness, the problem of the transfer of results from clinical trials to the individual patient was solved.

Clinical Competence↗
PubMed1990

From gene to chromosome: organization levels defined by the interplay of transcription and replication in vertebrates.

In higher eukaryotes, gene activation is accompanied by an increased sensitivity to DNaseI over a domain that extends beyond the limits of the gene itself, or of the gene cluster to which it belongs. This increased sensitivity probably reflects both the partial decondensation of chromatin and an increased communication with the outside of the nucleus. In addition, gene activation usually causes a coreplication domain that extends much beyond the decondensation domain to switch to an early replication time in S phase. This switch is produced, at least in some cases, by an early firing of origins of replication situated in flanking condensed chromatin. Some of the recently identified DNA domains that tether chromosomal loops to the nuclear matrix do represent the borders of decondensation domains. They may also constitute pausing sites for replication forks. The different replication times of successive 200- to 400-kb regions along the genome may have been the basis for the observed long-term differentiation of very large genomes in domains of different overall sequence composition (G:C content and distribution of short repeated motifs). Chromosomal bands represent a low resolution picture of this pattern. Just like gene methylation, differential replication timing and the consequent compositional differentiation of the genome have probably contributed to making the management of very large genomes workable.

Animals↗
PubMed1990

Arctic adaptation in whale hemoglobin: interplay of carbon dioxide and temperature in the oxygen unloading.

The functional properties of hemoglobin from the whale Balaenoptera acutorostrata have been characterized as a function of pH, CO2, organic phosphates and temperature. Carbon dioxide effect does not depend on the presence of organic phosphates such as 2,3-DPG and P6-inositol while it is strongly affected by temperature, so that at 37 degrees C it is completely abolished. This, together with the very small delta H of oxygen binding (delta H = -4 to -2 Kcal/mol of oxygen at pH 7.4) has been physiologically interpreted on the basis of the specific metabolic needs of fins and tail which are the place of a great muscular activity.

Adaptation, Physiological↗
PubMed1990

Intestinal calcium absorption. Interplay of paracellular and cellular pathways.

Intestinal absorption of calcium as characterized by studies in the rat follows both mediated mechanisms through enterocytes as well as fluxes between epithelial cells. Data summarized in this review suggests that the extracellular or paracellular route in distal small intestine plays a dominant role in calcium absorption at luminal calcium concentrations above 1 mM; proximal small intestine and cecum/colon show a much greater dependence on cellular translocation processes. The wide spectrum of paracellular:cellular transport ratios found in the intestine suggests a well-adapted mechanism to minimize energy expenditure for calcium absorption in the presence of adequate dietary calcium with capacity for efficient calcium scavenging when dietary supplies are limited. No evidence to date supports a role for vitamin D in the control of paracellular calcium absorption. Other mechanisms regulating paracellular calcium absorption will undoubtedly become a significant new area for future inquiry.

Animals↗