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At least 397 records · Page 22Linked to original sources

PubMed1999

Effects of experimental chemoendocrine therapy with a combination of a pure antiestrogen and 5-fluorouracil on human breast cancer cells implanted in nude mice.

The antitumor effects of an experimental chemoendocrine therapy combining a new pure antiestrogen ICI 182780 and 5-fluorouracil (5-FU) were studied on MCF-7 human breast cancer cells implanted in nude mice. ICI 182780 had a dose-dependent antitumor activity, which was potentiated by the concomitant use of 5-FU. When compared with the control group, the estrogen receptor (ER) level in the ICI 182780 group was lower and that in the combination group was markedly lower. Cell cycle analysis by flow cytometry (FCM) resulted in a lower percentage of S-phase cells (%S) in the treated mice. No significant difference was observed in the 5-FU concentrations in tumor cells, while the 5-FU content in RNA was significantly higher in the combination group. The changes in free thymidylate synthetase (TS) concentration indicated TS synthesis after the administration of 5-FU to be more greatly suppressed in the combination group than in the 5-FU group. These results suggest that ICI 182780 and 5-FU exert their combination effect mainly on ER-positive cells, and that the suppression of TS synthesis in tumor cells and the potentiation of the 5-FU-induced metabolic dysfunction of RNA are thus involved in the mode of action of this combination therapy.

Animals↗

PubMed2003

Growth hormone treatment in a girl with Prader Willi syndrome.

Prader Willi syndrome (PWS) is a rare endocrine-metabolic disorder that is characterised by neonatal hypotonia, hyperphagia, marked obesity, short stature, hypogonadism and behavioural problems. 7-20% percent of these children develop diabetes mellitus. A large number of individuals with PWS show growth hormone (GH) deficiency. Recent studies indicate beneficial effects of GH replacement therapy not only for their linear growth but also for correction of metabolic dysfunction. In the present communication this article details about the therapeutic outcome in a girl with PWS who received recombinant growth hormone (rGH), Genotropin. Some carry-over therapeutic benefits have been observed even after discontinuation of rGH.

Adolescent↗

PubMed2004

Neuroprotective strategies for HIV-1 associated dementia.

The human immunodeficiency virus-1 (HIV-1) commonly affects cognitive, behavioral and motor functions during the disease course. The neuropathogenesis of viral infection revolves around neurotoxins produced from infected and immune-activated mononuclear phagocytes (MP; perivascular macrophages and microglia). Direct infection of neurons occurs rarely, if at all. Neurologic disease arises in part as a consequence of MP metabolic dysfunction. Although the advent of highly active antiretroviral therapy (HAART) has attenuated the incidence and severity of neurologic disease, it, nonetheless, remains a common and disabling problem for those living with HIV-1 infection. Adjunctive therapies are currently designed to ameliorate clinical outcomes and are included in the therapeutic armamentarium. Anti-inflammatory drugs that inhibit cytokines, chemokines and interferons linked to neurodegenerative processes can significantly ameliorate neuronal function. HIV-1 neurotoxins have the unique ability to up-regulate glycogen synthase kinase-3beta (GSK-3beta) activity that in turn elicits neuronal apoptosis. GSK-3beta inhibitors are neuroprotective in animal models of Neuro AIDS. They are also currently in Phase 1 clinical trials designed for safety and tolerability in patients with HIV-1 infection. Neurotrophins are only beginning to be realized for their therapeutic potential in HIV-1 associated neurologic disease. This review article provides a broad overview of neuroprotective strategies for HIV-1 infection and details how such strategies act and may be implemented for treatment of human disease.

AIDS Dementia Complex↗

PubMed1998

Reverse redistribution of Tc-99m-tetrofosmin in exercise myocardial SPECT in patients with hypertrophic cardiomyopathy.

We examined the usefulness of Tc-99m-tetrofosmin in detecting exercise induced perfusion abnormalities in patients with hypertrophic cardiomyopathy (HCM) and to clarify time-related changes in myocardial distribution of Tc-99m-tetrofosmin after a single injection. We studied 44 consecutive patients with HCM by means of exercise/rest Tc-99m-tetrofosmin single photon emission computed tomography (SPECT). After injecting 370 MBq of Tc-99m-tetrofosmin at the peak exercise, the early SPECT imaging was performed at 30 min (EX-30) and the delayed imaging at 180 min (EX- 180). Immediately after the delayed imaging, 740 MBq of Tc-99m-tetrofosmin was injected in the resting state, and the rest SPECT imaging was performed 30 min later. Exercise-induced regional perfusion defects and/or apparent reversible left ventricular cavity dilation were identified in 26 (68.2%) of the 44 patients. When EX-30 images and EX-180 images were compared, reverse redistribution was confirmed in 36 patients (81.8%). Reverse redistribution was detected most frequently in the septal portion of the anterior wall, followed by the septal portion of the posterior wall and the septum. Exercise/rest Tc-99m-tetrofosmin myocardial imaging was a useful method for assessing myocardial perfusion abnormalities in patients with HCM. Reverse redistribution was detected very frequently on early and delayed images of exercise. We assumed that reverse redistribution may reflect a retention disorder of Tc-99m-tetrofosmin caused by some metabolic dysfunction of myocytes.

Cardiomyopathy, Hypertrophic↗

PubMed1999

Enteral histaminosis: Clinical implications.

There is increasing evidence that enteral histaminosis is a major cause of food intolerance resulting from dysfunctional metabolism of endogenous histamine in certain food stuffs. However, this phenomenon has been poorly characterised and, due to the lack of epidemiological data, the existence of this condition has been underestimated, which may lead to incorrect diagnosis. This short commentary highlights a stricter regimen of diagnostic procedure in order to take into account the many causes of food intolerance. The underlying mechanisms ascribed particularly to non-immunologically food reactions require more rigorous research and further work is vital.

Clinical Protocols↗

PubMed2004

[Teutschländer disease. A rare benign differential diagnosis of proliferative space-occupying lesions in the periarticular soft tissue].

The tumoral calcinosis (synonym: Teutschländer disease) is a very rare benign metabolic dysfunction of unknown etiology. It manifests principally as massive subcutaneous soft tissue deposits of calcium phosphate near the large joints and is also characterized by slow progressive growth. Causally, a disturbance of the calcium and phosphate metabolism/balance with, among others, autosomal dominant heredity is suspected. It appears frequently in the black African population in all age groups, but preferentially in the 1st and 2nd decades of life. Medical help is most frequently sought because of increasing tumor size causing displacement and consecutive pain as well as decreased joint play. We present here a case of Teutschländer disease in a 50-year-old woman on long-term hemodialysis and describe the clinical, radiological, and pathological signs of this rare disease. Subsequently, speculative etiology, differential diagnostic considerations as well as the therapeutic interventions for tumoral calcinosis are discussed taking into consideration the current literature.

Calcinosis↗

PubMed2006

Increased colorectal permeability in patients with severe sepsis and septic shock.

OBJECTIVE: To develop a method for the assessment of colorectal permeability in septic patients. DESIGN AND SETTING: Observational study in ICUs at two university hospitals. PARTICIPANTS: Nine patients with septic shock and abdominal focus of infection, 7 with severe sepsis and pulmonary focus and 8 healthy subjects. MEASUREMENTS AND RESULTS: Colorectal permeability was assessed as the initial appearance rate of (99m)Tc-DTPA in plasma after instillation into the rectal lumen and as the cumulative systemic recovery at 1h. To calculate the latter, volume of distribution and renal clearance of (99m)Tc-DTPA was estimated by an i.v. bolus of (51)Cr-EDTA. The initial rate of permeability was increased in patients with septic shock and severe sepsis compared with controls [29.0 (3.7-83.3), 20.6 (3.6-65.5) and 6.0 (2.2-9.6)cpm ml(-1)min(-1), respectively, p<0.05)] with a positive linear trend (r (2)=0.27, p=0.01) and correlated to L-lactate concentrations in the rectal lumen (r (2)=0.39, p<0.05). The cumulative permeability was also increased in patients with septic shock and severe sepsis compared with controls [2.07 (0.05-15.7), 0.32 (0.01-1.2) and 0.03 (0.01-0.06) per thousand, respectively, p<0.01] and correlated to the initial permeability rate (r (2)=0.26, p=0.01). CONCLUSIONS: In septic patients, the systemic recovery of a luminally applied marker of paracellular permeability was increased and related to the luminal concentrations of L-lactate and possibly to disease severity. This suggests that the assessment of colorectal permeability by systemic recovery of (99m)Tc-DTPA is valid and that metabolic dysfunction of the mucosa contributes to increased permeability of the large bowel in patients with severe sepsis and septic shock.

Adult↗

PubMed2003

Comparison of conventional and diffusion-weighted MRI and proton MR spectroscopy in patients with mitochondrial encephalomyopathy, lactic acidosis, and stroke-like events.

The mechanism of neurological disturbances in patients with mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) is controversial. We studied 12 patients with MELAS using conventional and diffusion weighted MRI (DWI) and MR spectroscopy (MRS), to look at the physiopathology of the stroke-like events. Although conventional MRI showed lesions in all patients, DWI was more sensitive. One patient did not show high signal on DWI 48 h after a from stroke-like episode, but MRS demonstrated a lactate peak in left occipital lobe; 2 weeks after the attack, high signal was demonstrated on the right frontal lobe where MRS had shown a lactate peak. Our findings suggest a possible predictive ability of (1)H-MRS, in showing early MELAS lesions and supports the hypothesis that mitochondrial metabolic dysfunction may precedes abnormalities on DWI.

Adolescent↗

PubMed2026

Allelochemical signaling and phytohormone crosstalk in plants: molecular mechanisms and implications for sustainable weed management.

Phytotoxic effects from allelopathy occur due to signaling pathways that induce alterations in hormonal balance within the plants, thereby hindering weed growth. Signaling crosstalk between various hormones and signaling pathways (Ca2⁺, MAPK, ROS) is involved in the molecular response mechanisms found through omics. Utilizing such mechanisms would help develop new environmentally friendly methods for sustainable weed management. Allelopathy serves as an essential component of plant-plant interaction via controlling the secretion of secondary metabolites (allelochemicals), which affect the growth, development, and physiological activity of nearby plants. The latest findings indicate that allelochemicals disturb phytohormone balance and signaling pathways resulting in oxidative stress, metabolism dysfunctions, cellular processes disturbances, and eventually inhibiting the growth of target weed species. Molecular biology progress and omics techniques brought information about the sophisticated regulation processes involved in allelopathic interactions. This review summarizes the information about the molecular mechanism of weed suppression mediated by allelopathy with the emphasis on allelochemical perception, phytohormone signaling, ROS responses, and evidence obtained by the application of transcriptomics, proteomics, metabolomics, and other omics-based studies. In addition, it introduces novel approaches, such as rhizosphere engineering, nanotechnologies, and genome editing, which may improve the effectiveness and reliability of allelopathic weed suppression. Overall, these achievements provide prospects for creating a new generation of weed control technologies that are sustainable, environmentally friendly, and climate-adaptive.

Plant Growth Regulators↗

PubMed2026

Effects of 12 weeks of resistance and concurrent training with graded protein intakes on lipid profile, kidney and liver biomarkers in middle-aged to older women.

PURPOSE: To examine secondary lipid, kidney-related, and liver-enzyme responses to three protein intakes during resistance training (RT) alone or the same RT plus cycling (CT) in middle-aged to older women. METHODS: In this randomized 2×3 factorial trial, 108 women aged 40-77 years were assigned to RT or CT and 0.8, 1.6, or 2.2 g kg-1 d-1 protein for 12 weeks. This complete-case secondary analysis included 83 participants. Linear mixed-effects models tested Time × Training, Time × Protein, and Time × Training × Protein effects, with false-discovery-rate-adjusted omnibus tests and Holm-adjusted contrasts. RESULTS: Triglycerides, total cholesterol, LDL-C, and apolipoprotein B decreased and HDL-C increased in all conditions. Lipid changes differed by protein condition, and several were more favorable with CT; however, CT comprised RT plus additional cycling and greater exercise exposure. Urea, blood urea nitrogen, creatinine, the blood urea nitrogen-to-creatinine ratio, and cystatin C increased, whereas three eGFR estimates decreased. Responses differed mainly between 0.8 and the two higher protein conditions, with little evidence of differences between 1.6 and 2.2 g kg-1 d-1. ALT, AST, and GGT differed by protein condition; AST and GGT also showed training-dependent responses. CONCLUSIONS: The dietary and exercise interventions modified lipid and clinical-chemistry responses. Because energy and food composition were not fully matched and CT added cycling to RT, the findings do not isolate protein dose or exercise modality. Changes in eGFR estimates and liver enzymes do not establish organ injury or long-term safety.

Humans↗

PubMedDate not supplied

A common PEX1 frameshift mutation in patients with disorders of peroxisome biogenesis correlates with the severe Zellweger syndrome phenotype.

Peroxisome biogenesis disorders are a heterogeneous group of human neurodegenerative diseases caused by peroxisomal metabolic dysfunction. At the molecular level, these disorders arise from mutations in PEX genes that encode proteins required for the import of proteins into the peroxisomal lumen. The Zellweger syndrome spectrum of diseases is a major sub-set of these disorders and represents a clinical continuum from Zellweger syndrome (the most severe) through neonatal adrenoleukodystrophy to infantile Refsum disease. The PEX1 gene, which encodes a cytoplasmic AAA ATPase, is the responsible gene in more than half of the Zellweger syndrome spectrum patients, and mutations in PEX1 can account for the full spectrum of phenotypes seen in these patients. In these studies, we have undertaken mutation analysis of PEX1 in skin fibroblast cell lines from Australasian Zellweger syndrome spectrum patients. A previously reported common PEX1 mutation that gives rise to a G843D substitution and correlates with the less severe disease phenotypes has been found to be present at high frequency in our patient cohort. We also report a novel PEX1 mutation that occurs at high frequency in Zellweger syndrome spectrum patients. This mutation produces a frameshift in exon 13, a change that leads to the premature truncation of the PEX1 protein. A Zellweger syndrome patient who was homozygous for this mutation and who survived for less than two months from birth had undetectable levels of PEX1 mRNA. This new common mutation therefore correlates with a severe disease phenotype. We have adopted procedures for the detection of this mutation for successful prenatal diagnosis.

ATPases Associated with Diverse Cellular Activitie↗

PubMed2006

Atherosclerotic risk factors and carotid stiffness in elderly asymptomatic HD patients.

Several studies showed that carotid atherosclerosis and stiffness are independent prognostic factors of cardiovascular morbidity and mortality in the general population and in end-stage renal disease patients. However, the impact of established risk factors on carotid structural and elastic properties in non-diabetic elderly hemodialysis patients with negative history for cardiovascular disease has not been fully elucidated. In this paper, we investigated the effect of established and potential risk factors on carotid atherosclerosis and stiffness. Thirty stable, non-symptomatic, non-diabetic patients, aged 65-years and older (mean age 71.4+/-4.15, range 65-79) on hemodialysis for more than 6 months, were included. All patients underwent B-mode ultrasonography of common carotid artery estimating intima-media wall thickness and wall-to-lumen ratio bilaterally and checking for the presence of plaques. Carotid elasticity was evaluated by compliance, distensibility, and the incremental elastic modulus (Einc), whereas systemic arterial stiffening was evaluated by the augmentation index provided by tonometry of radial artery. Our results showed that presence of carotid plaques and wall thickening were frequent findings in this population (76% and 73.3%, respectively) and they were positively associated with fibrinogen (P<0.005), diastolic blood pressure (P<0.004), visceral obesity (P<0.001) and bio-intact PTH (i-PTH) (P=0.03). Overall, systemic and carotid stiffness were strongly correlated with hs-CRP (P=0.018), serum ferritin (P=0.02) with age (P=0.03), lipids (P=0.03) and i-PTH (P=0.05). In conclusion, our findings show that stiffening and atherosclerosis in non-symptomatic elderly HD patients are very common and they are related not only to hemodynamic changes (diastolic blood pressure), inflammation (hs-CRP, fibrinogen, ferritin) or metabolic dysfunction (increased i-PTH, abnormal lipid profile), but also to abnormal fat deposition (increased waist to hip ratio and waist circumference). Considering the high morbidity and mortality of elderly patients, close monitoring of these parameters could be useful to prevent cardiovascular events.

Aged↗

PubMed2006

The mortality of MOP3 deficient mice with a systemic functional failure.

MOP3 (also known as BMAL1), a master regulator of circadian rhythm, plays important roles in the regulation of cell differentiation and general physical functions. In the present studies, MOP3 deficient mice had significantly reduced body weight and showed remarkable mortality around six months of age. The levels of AST, ALT, BUN, or UREA in the blood of about four month-old MOP3(-/-) mice were significantly higher than MOP3(+/-) or MOP3(+/+) littermates. However, no apparent pathological changes in the livers, hearts, lungs or kidneys of about four month-old MOP3(-/-) mice were observed. In addition, altered levels of white blood cells, lymphocytes, and platelets in peripheral blood of MOP3(-/-)mice were detected. The results presented herein with MOP3-deficient mice offered the basic principle for the essential roles of MOP3 in keeping normal survival abilities in mice. This study may have significant clinical impacts on the consideration about the abnormality of circadian rhythms and sleeping disorders caused physical and metabolism dysfunctions as well as the mortality.

ARNTL Transcription Factors↗

PubMed2006

Metabolic modulation of myocardial ischemia.

The metabolic pathways of the heart during normoxia and ischemia have been well studied. High plasma fatty acid concentrations and the myocardial accumulation of long-chain fatty acyl metabolites during ischemia correlate with increased morbidity and mortality. However, enhanced glucose use can maintain cell homeostasis, diminish ischemic injury, and be clinically beneficial. Metabolic modulators represent a new class of drugs with the potential to treat myocardial ischemia. They are ideal as adjunctive anti-ischemic therapy because they lack the hemodynamic consequences of traditional therapy and treat the underlying metabolic dysfunction that leads to contractile failure and arrhythmias. Clinical studies have demonstrated their efficacy in acute and chronic settings. It is anticipated that there will be greater utilization of this new class of agents in the near future.

Adrenergic beta-Antagonists↗

PubMed2003

Adiponectin: systemic contributor to insulin sensitivity.

Adipocyte-specific secreted molecules, termed adipokines, have dispelled the notion of adipose tissue as an inert storage depot for lipids, and highlighted its role as an active endocrine organ that monitors and alters whole-body metabolism and maintains energy homeostasis. One of these adipokines, adiponectin (also known as Acrp30, AdipoQ, and GBP28), has gained significant attention recently as a mediator of insulin sensitivity. Many clinical reports and genetic studies over the past few years demonstrate decreased circulating levels of this hormone in metabolic dysfunction, such as obesity and insulin resistance, in both humans and animal models. Pharmacologic adiponectin treatments in rodents increase insulin sensitivity, although the primary site and detailed mechanism of action is yet to be determined. The phenotypes of adiponectin-deficient and transgenic adiponectin-overproducing animal models underscore the role of adiponectin in the maintenance of glucose and lipid homeostasis.

Adiponectin↗

PubMed2001

Diabetic Lumbosacral Polyradiculoneuropathies.

The pathogenic basis and treatment of diabetic polyradiculoneuropathy is a source of recent controversy as there may be two or more distinct forms of diabetic polyradiculoplexopathy. We believe that the following two categories of diabetic polyradiculoneuropathy can be made on the basis of clinically differences: 1) the more common asymmetric, painful polyradiculoneuropathy; and 2) the rare symmetric, painless, polyradiculoneuropathy. The asymmetric, painful form (also known as diabetic amyotrophy) may have an autoimmune basis, but the etiology is not clear. The natural history for diabetic amyotrophy is spontaneous improvement. Nevertheless, various immunotherapies (eg, corticosteroids and intravenous immunoglobulin (IVIg) have been tried with subsequent improvement in symptoms. Treatment is reserved only for patients with severe ongoing pain, given the significant side effects of these medications in those patients with diabetes. Prednisone and IVIg may help alleviate the pain associated with diabetic amyotrophy. Relief of pain can help patients begin physical therapy earlier, however, there are no prospective, blinded, controlled studies that demonstrate that these treatments lead to an earlier and better recovery of muscle strength compared with the natural history of the disorder. The symmetric, painless form of diabetic polyradiculoneuropathy may in fact represent chronic inflammatory demyelinating polyneuropathy (CIDP) occurring in a patient with diabetes mellitus (DM). Patients with idiopathic CIDP may improve various immunomodulating therapies, including corticosteroid treatment, plasma exchange (PE), and IVIg. In this regard, patients with the symmetric, painless, proximal diabetic polyradiculoneuropathy may also respond to corticosteroids, plasma exchange, IVIg, azathioprine, or cyclophosphamide. However, as with diabetic amyotrophy, some patients improve spontaneously without treatment. In still other patients, the neuropathy appears unresponsive to immunotherapy. In such patients, this polyradiculoneuropathy might be caused by metabolic dysfunction associated with DM. Unfortunately, from a clinical, laboratory, and electrophysiologic standpoint, it is impossible to distinguish the patients with a symmetric, painless diabetic polyradiculoneuropathy who might respond to therapy. A trial of PE can be useful in identifying patients who might have a polyradiculoplexopathy that is responsive to immunotherapy. If patients respond to PE, they may continue to receive intermittent exchanges or be switched over to prednisone or IVIg.

Journal Article↗

PubMed1975

Revascularization after 3 hours of coronary arterial occlusion: effects on regional cardiac metabolic function and infarct size.

Two experimental series of closed chest dogs were compared: Group A (five dogs with 7 days of continuous occlusion of the proximal left anterior descending coronary artery); and Group B (six dogs with 7 days of reperfusion after 3 hours of acute occlusion of the same artery). Hemodynamic measurements, ventricular wall motion, coronary sinus blood flow and regional metabolism in both coronary occluded and nonoccluded segments of the left ventricle were measured sequentially. The infarct size was characterized by detailed histopathologic analysis. In the control dogs (Group A), mechanical and metabolic function remained severely depressed after 7 days of occlusion, and mean infarct size was 31.6 percent. In Group B, significant mechanical and metabolic dysfunction developed during 3 hours of occlusion and did not improve during the 1st hour of reperfusion. However, after 7 days of reperfusion, function returned to near preocclusion level. Mean infarct size was 14.2 percent, but in two of the six dogs infarct size was 43 percent and 23 percent, respectively. The study confirmed the unstable character of the early phase of reperfusion, attributed to cell swelling, edema and hemorrhages that resulted in inadequate coronary reflow, arrhythmias and functional derangements. Prolonged reperfusion for 7 days reduced mean infarct size and improved cardiac function.

Animals↗

PubMed1987

Adequacy of central hemodynamics versus restoration of circulation in the survival of patients with acute aortic thrombosis.

Acute aortic thrombosis is an infrequent clinical occurrence, but when it does occur, it is a true cardiovascular catastrophe. Our experience with 34 patients over a 12 year period was reviewed and factors influencing outcome were analyzed. Seventeen women and 17 men had various clinical presentations, although 74 percent of the patients had the classic picture of ischemia. Preoperative assessment of left ventricular function was carried out in all but one patient with intraoperative and perioperative monitoring to guide therapy in addition to revascularization procedures. While extent of the preexisting disease and number of additional operations did influence the outcome, the predominant factor for survival was the left ventricular functional state perioperatively. Fifteen of the 16 patients with adequate left ventricular function survived, whereas 15 of the 17 patients with a failing myocardium died (88 percent). Extraanatomic operations are preferable in patients with demonstrated inadequate left ventricular function. Expeditious restoration of circulation alone does not ensure a favorable outcome. The key to successful therapy is understanding, preventing, and effectively treating the mechanical and metabolic dysfunction of the heart. Review of the literature on acute aortic thrombosis revealed only few isolated case reports except for a recent report of eight patients. Our report of 34 patients over a 12 year period represents the largest experience to date from a single institution. Detailed analysis of hemodynamic parameters and the significance of determination of left ventricular function has not been reported so far in this subset of critically ill patients.

Acute Disease↗