Nifedipine Reduces the Colonic Motor Response to Eating in Patients with the Irritable Colon Syndrome

Patients with the irritable colon syndrome have an exaggerated and/or prolonged colonic motor response to eating. This is believed to be the cause of their postprandial complaints. Since the flux of calcium ions across cell membranes plays a major role in the contractions of the gastrointestinal smooth muscle, we investigated the effect of nifedipine, a calcium channel blocker, on the gastrocolonic response in nine patients with the irritable colon syndrome. Colonic myoelectric and contractile activity was recorded during fasting and after a 1000-cal mixed meal, either with or without nifedipine (20 mg sublingually) administration. Nifedipine reduced the postprandial increase of both spike potential activity and motility index. This effect of acute administration of the drug provides rational support to test nifedipine in clinical trials as a possible means for treating the irritable colon syndrome.     

Understanding the knowledge,attitudes and beliefs of community-dwelling older adults and their carers about the modification of oral medicines: A qualitative interview study to inform healthcare professional practice

BackgroundOral medicines are commonly modified (e.g. tablets split/crushed) to meet the dosing and swallowing requirements of older adults. However, there is limited research investigating the opinions of community-dwelling patients and carers about medicine modification.ObjectivesThe aim of this study was to investigate the views of community-dwelling older adults and their carers about oral medicine modification.MethodsSemi-structured, face-to-face interviews were conducted with community-dwelling older adults and carers of older adults who experienced difficulty swallowing medicines, or who required medicines to be modified. Participants were recruited from purposively selected community pharmacies using a combination of purposive, convenience and snowball sampling. Interviews were audio-recorded, transcribed verbatim and analysed thematically. The Francis method governed when data saturation had been reached.ResultsTwenty-six interviews (13 patients, 13 carers) were conducted (76.9% female, median length 11 min (IQR 8–16 min)). Four themes emerged from the data: variation in medical needs and preferences; balancing acceptance and resignation; healthcare professional engagement and; opportunities for optimising formulation suitability. The heterogeneity of medical conditions experienced by community-dwelling older adults resulted in a variety of modifications being required. Patients and carers are accepting of their medications and formulations. However, when challenges arise, they tend to feel resigned to coping within the constraints of the current medication regimen, resulting in a lack of focused communication with healthcare professionals. Thus, healthcare professionals were unaware of their difficulties and unable to offer advice or solutions.ConclusionHealthcare professionals must engage proactively with this group. Whilst a holistic approach to medication management is ideal, the disadvantage is that no single healthcare professional may identify this as their responsibility. Whilst the input and expertise of all healthcare professionals will be required, as medication experts, the pharmacy profession should take ownership and become the champion of, and for, the patient.     

The management of patients with acute ischemic stroke while on direct oral anticoagulants (DOACs): data from an Italian cohort and a proposed algorithm

Journal of Thrombosis and Thrombolysis - Approximately 1–2% of patients with non-valvular atrial fibrillation have an acute ischemic stroke (AIS) while on direct oral anticoagulant (DOAC)...     

Effect of the inserted active-site-covering lid loop on the catalytic activity of a mutant B. subtilis γ-glutamyltransferase (GGT)

γ-Glutamylpeptides are compounds derived from the acylation of an amino acid or a short peptide by the γ-carboxyl carbon of the side chain of glutamic acid. Due to their altered chemico-physical and organoleptic properties, they may be interesting substitutes or precursors of parent compounds used in pharmaceutical, dietetic and cosmetic formulations. Some of them are naturally occurring flavor enhancers or are endowed with biological activities. Enzymatic approaches to the synthesis of γ-glutamyl derivatives based on the use of γ-glutamyltransferases (GGTs, EC 2.3.2.2) have been proposed, which should be able to alleviate the problems connected with the troublesome and low-yielding extraction from natural sources or the non-economical chemical synthesis, which requires protection/deprotection steps. With the aim of overcoming the current limitations in the use of GGTs as biocatalysts, a mutant GGT was investigated. The mutant GGT was obtained by inserting the active-site-covering lid loop of the E. coli GGT onto the structure of B. subtilis GGT. With respect to the wild-type enzyme, the mutant showed a more demanding substrate specificity and a low hydrolase activity. These results represent an attempt to correlate the structural features of a GGT to its different activities. However, the ability of the mutant enzyme to catalyze the subsequent addition of several γ-glutamyl units, inherited by the parent B. subtilis GGT, still represents a limitation to its full application as a biocatalyst for preparative purposes.

A mutant γ-glutamyltransferase with improve transpeptidase activity was obtained by inserting the active site-covering lid loop on an enzyme naturally lacking it.     

C-Fos expression as a molecular marker in corticotropin-releasing factor-induced seizures

Expression of Fos-like protein has been shown to increase after seizures in several types of experimentally induced epilepsies. The intracerebroventricular (icv) injection of murine corticotropin-releasing factor (CRF) in rats (10 μg), shows an electroencephalographic (EEG) spiking activity restricted to the amygdaloid-hippocampal area. This EEG seizure pattern represents a unique model of localized epileptic activity induced by a neuropeptide. C-fos expression after icv CRF has been considered a useful tool in mapping areas involved in stress and in seizure activity. Our results show that 1 μg and 10 μg CRF are able to induce c-fos activation in several brain areas. Moreover, the present study not only details c-fos expression increase in brain areas directly involved in spiking activation, such as the amygdaloid-hippocampal region, but also maps the possible contribution of other regions to seizure manifestations. © 1996 Wiley-Liss, Inc.     

Challenges and recommendations when selecting empirical antibiotics in patients with cirrhosis

There is abundant evidence that bacterial infections are severe complications in patients with cirrhosis,being the most frequent trigger of acute-on-chronic liver failure and causing death in one of every four patients during hospitalization.For these reasons,early diagnosis and effective treatment of infections are mandatory to improve patient outcomes.However,treating physicians are challenged in daily practice since diagnosing bacterial infections is not always straightforward.This situation ...     

Protective effects of beet (Beta vulgaris) leaves extract against oxidative stress in endothelial cells in vitro

Beetroot is an herb used worldwide as a food product, raw material for food industry, ethanol production and source of food coloring. Beet leaves are an unconventional food with antioxidant properties, which might neutralize reactive oxygen species (ROS) induced by oxidized Low‐Density Lipoprotein (LDL) present in dyslipidemias. This study aimed to elucidate the effects of beet leaves on the suppression of LDL oxidative processes. Beet leaves extract was produced, characterized, and tested for its antioxidant capacity using endothelial cells in vitro. A model of human umbilical vein endothelial cells was used in various tests, including viability assay, molecular analysis of antioxidant genes, ROS labeling, and macrophage adhesion assay. The extract improved the antioxidative protection of endothelial cells against different agents including oxidized LDL‐cholesterol and H₂O₂. It acted on ROS directly due to its high content of natural antioxidants, but also due to the activation and improvement of cellular defenses such as Superoxide dismutase 1, Superoxide dismutase 2, and catalase. The inhibition of LDL‐mediated oxidative effects on endothelial cells may turn this unconventional food a functional food with great potential for phytotherapy of atherosclerosis as an adjuvant for medicinal treatments.     

Apolipoprotein E alleles in nonagenarian subjects in the Belfast Elderly Longitudinal Free-living Ageing Study (BELFAST)

The ApoE gene has three alleles coding for the proteins apoE2, apoE3 and apoE4. E4 has been reported to be associated with hypercholesteraemia, ischaemic heart disease, age-related cognitive decline and Alzheimer's disease. Conversely, the E2 allele has been associated with longevity in French centenarians and their siblings. In this study, we have assessed any shift in the ApoE genotypes in nonagenarian subjects from Belfast where there is a high intrinsic incidence of cardiovascular disease. ApoE phenotypes were determined by electrofocusing and immunoblotting in 114 Senieur-approximated subjects >90 years old and compared with 2071 subjects, 30--65 years of age, recruited from the same geographical area by the MONItoring of CArdiovascular trends study group in Belfast (MONICA). The E4 allele was reduced in the nonagenarian group (X(2)=11.1; P=0.0006), the E3 unchanged and E2 frequency was increased (X(2)=4.0; P=0.047). These results suggest that longevity is negatively associated with the E4 allele and may be associated with carriage of E2.     

Minimally invasive treatment of synchronous colorectal tumours

In patients with colorectal cancers synchronous neoplastic lesions are an increasingly frequent finding at preoperative staging; 3% of the cases are other cancers while 33-35% of the synchronous lesions are villous adenomas. The treatment of most colorectal adenomas can be performed by endoscopic poplypectomy. In 5% of cases there are synchronous colorectal lesions also requiring surgical treatment. From January 1995 to June 2007 we treated 5 patients with rectal lesions by transanal endoscopic microsurgery (TEM) together with a laparoscopic colectomy for the presence of synchronous lesions at the "Clinica Chirurgica Generale e d'Urgenza" of the University of Perugia,. Surgical timing involved performing a sequential exeresis characterised by a cancer resection, followed by resection of the voluminous adenoma: TEM for rectal cancer followed by a laparoscopic right hemicolectomy with an extracorporeal anastomosis for a voluminous villous adenoma (1 patient) and laparoscopic right hemicolectomy with an extracorporeal anastomosis for cancer followed by TEM for a voluminous villous adenoma (2 patients). One patient with left colon cancer associated with a voluminous villous rectal adenoma first underwent TEM for the rectal adenoma and then a left laparoscopic hemicolectomy with an extracorporeal anastomosis in order to ease the transit of the circular mechanical stapler. Another patient with rectal and right colon adenomas first underwent TEM for a voluminous rectal sessile adenoma and later a right hemicolectomy. The use of this minimally invasive approach allowed rectum preservation and less invasive surgery.