Cellular and physiological effects of C-peptide.

In recent years, accumulating evidence indicates a biological function for proinsulin C-peptide. These results challenge the traditional view that C-peptide is essentially inert and only useful as a surrogate marker of insulin release. Accordingly, it is now clear that C-peptide binds with high affinity to cell membranes, probably to a pertussis-toxin-sensitive G-protein-coupled receptor.

C-peptide reverses TGF-beta1-induced changes in renal proximal tubular cells: implications for treatment of diabetic nephropathy.

The crucial pathology underlying progressive chronic kidney disease in diabetes is tubulointerstitial fibrosis. Central to this process is epithelial-mesenchymal transformation (EMT) of proximal tubular epithelial cells driven by maladaptive transforming growth factor-beta1 (TGF-beta1) signaling. Novel signaling roles for C-peptide have recently been discovered with evidence emerging that C-peptide may mitigate microvascular complications of diabetes.

The molecular interactions between filtered proteins and proximal tubular cells in proteinuria.

Proteinuria is associated with progressive chronic kidney disease and poor cardiovascular outcomes. Exposure of proximal tubular epithelial cells to excess proteins leads to the development of proteinuric nephropathy with tubular atrophy, interstitial inflammation and scarring. Numerous signalling pathways are activated in proximal tubular epithelial cells under proteinuric conditions resulting in gene transcription, altered growth and the secretion of inflammatory and profibrotic mediators.

The Hypertension in Diabetes Study (HDS): a catalyst for change.

Hypertension is now established as a major risk factor for premature cardiovascular morbidity and mortality in people with Type 2 diabetes and all modern treatment guidelines recommend the routine treatment of hypertension in these patients. However, these developments have been relatively recent. Only a decade ago, outside of small studies in patients with nephropathy, there was little evidence with regard to the efficacy and safety of treating elevated blood pressure in people with Type 2 diabetes.

Catecholamine inotrope resuscitation of antibiotic-damaged staphylococci and its blockade by specific receptor antagonists.

The increasing use of antibiotic-coated catheters, such as those containing rifampin or minocycline, has led to a decrease in catheter colonization by staphylococci but not to a decrease in the incidence of catheter-related bloodstream infection (BSI). Because catheters are used for the administration of catecholamine inotropes to maintain cardiac function, we examined whether 2 commonly employed inotropes, dopamine and norepinephrine, could affect bacterial viability after exposure to rifampin and minocycline. Rifampin inhibition and minocycline inhibition of staphylococcal growth could be reversed by exposure to dopamine or norepinephrine as a result, in part, of catecholamine-mediated increased provision of host-sequestered iron.

Patients' experiences and perceptions of medical student candidates sitting a finals examination.

Background: The Final Professional Examination for medical students at Leicester Medical School involves the use of real patients, and senior clinicians assess students over a series of consultations with these patients. What the patients themselves think of the students is not known.

Aims: This qualitative study identifies the perceptions and opinions which patients who have been used in this examination have of the student candidates, and whether these may be used to enhance the training of medical students.

Influence of dietary catechols on the growth of enteropathogenic bacteria.

The dietary constituents that may act, in the broadest sense, as co-factors to enable bacterial enteropathogens to replicate in gastrointestinal environments are still largely unknown. Recent work has demonstrated that certain non-nutritional components of food, such as the catecholamines, can contribute to the ability of Gram-negative pathogens to replicate in iron-restrictive media that may be reflective of gastrointestinal environments. The present report examines whether other, non-catecholamine, dietary catechols, which occur widely in plant foods, can also influence enteropathogen growth in an iron-restrictive environment such as might be found in the gastrointestinal tract.

Blockade of catecholamine-induced growth by adrenergic and dopaminergic receptor antagonists in Escherichia coli O157:H7, Salmonella enterica and Yersinia enterocolitica.

Background: The ability of catecholamines to stimulate bacterial growth was first demonstrated just over a decade ago. Little is still known however, concerning the nature of the putative bacterial adrenergic and/or dopaminergic receptor(s) to which catecholamines (norepinephrine, epinephrine and dopamine) may bind and exert their effects, or even whether the binding properties of such a receptor are similar between different species.

Results: Use of specific catecholamine receptor antagonists revealed that only alpha, and not beta, adrenergic antagonists were capable of blocking norepinephrine and epinephrine-induced growth, while antagonism of dopamine-mediated growth was achieved with the use of a dopaminergic antagonist.

The prospective, randomized investigation of the safety and efficacy of telmisartan versus ramipril using ambulatory blood pressure monitoring (PRISMA I).

Objective: To compare the efficacy and safety of once-daily telmisartan and ramipril on blood pressure (BP) reductions during the last 6 h of the dosing interval.

Patients And Methods: In a prospective, randomized, open-label, blinded-endpoint study using ambulatory BP monitoring, 801 patients with mild-to-moderate hypertension were randomly assigned to once-daily treatment with telmisartan 80 mg for 14 weeks or ramipril 5 mg for 8 weeks and then force titrated to ramipril 10 mg for the last 6 weeks. Primary endpoints were the reduction from baseline in the last 6-h mean ambulatory systolic BP (SBP) and diastolic BP (DBP).

Recent hypertension trials: implications and controversies.

The pharmacologic treatment of hypertension has been extensively studied by clinical trials. These studies have provided definitive evidence of a treatment benefit, and the weight and consistency of the clinical evidence has led to uniformity in many aspects of treatment recommendations worldwide. However, controversies remain-in particular, whether specific classes of drug therapy offer benefits for cardiovascular disease prevention beyond the expected benefits of blood pressure lowering per se.

Ciliary beat pattern is associated with specific ultrastructural defects in primary ciliary dyskinesia.

Background: The main symptoms of primary ciliary dyskinesia (PCD) are nasal rhinorrhea or blockage and moist-sounding cough. Diagnosis can be difficult and is based on an abnormal ciliary beat frequency, accompanied by specific abnormalities of the ciliary axoneme. It is unknown whether determining ciliary beat pattern related to specific ultrastructural ciliary defects might help in the diagnosis of PCD.

Growth inhibition by the muscarinic M(3) acetylcholine receptor: evidence for p21(Cip1/Waf1) involvement in G(1) arrest.

We have assessed the growth response of Chinese-hamster ovary (CHO) cells to activation of recombinantly expressed G-protein-coupled muscarinic M(2) or M(3) acetylcholine receptors (AChRs). We show that activation of these receptors leads to divergent growth responses: M(2) AChR activation causes an increase in DNA synthesis, whereas M(3) AChR activation causes a dramatic decrease in DNA synthesis. We have characterized the M(3) AChR-mediated growth inhibition and show that it involves a G(1) phase cell-cycle arrest.

Changes in serum vascular endothelial growth factor following initiation of estrogen replacement after hysterectomy and oophorectomy.

Background: Vascular endothelial growth factor has been shown to play an important role in preservation and restoration of endothelial integrity. Similar effects on endothelial function have been described with estrogen replacement. This poses the question whether some of the mechanisms ascribed to estrogen are in fact vascular endothelial growth factor mediated.

The vaccinia virus E3L protein interacts with SUMO-1 and ribosomal protein L23a in a yeast two hybrid assay.

We report the results of a two-hybrid study which identified clones from a HeLa cDNA library that interact with the vaccinia virus protein E3L. These clones encode the nuclear protein SUMO-1 (also known as PIC-1, sentrin or GMP-1); the cytoplasmic ribosomal protein L23a; and a small peptide sequence of unknown significance.

Examining consent within the patient-doctor relationship.

The notion of consent which rose to the forefront in biomedical ethics as an attempt to safeguard patients' autonomy, is relatively new. The notion itself requires qualification, for it precludes neither duress nor ignorance. More seriously, I argue here that consent is redundant except in situations where paternalism prevails.

Alterations in airway wall properties in infants with a history of wheezing disorders.

Airway diameter and airway wall mechanics (compliance) are important determinants of flow limitation and wheezing. We have previously used the high-speed interrupter technique (HIT) to measure input impedance (Zin) in infants at frequencies up to 900 Hz, including antiresonance phenomena, which are known to be related to wave propagation velocity, and have shown that the frequency at which the first antiresonance occurs (f(ar,1)) is a function of airway wall compliance. We aimed to determine whether f(ar,1) (and thus airway wall compliance) was different in infants with a history of wheezing disorders.