Hemorheology, melatonin and pinealectomy. What's the relationship? An experimental study

The circadian rhythm of stroke and myocardial infarction (MI) may be related to the circadian rhythm of melatonin, and erythrocyte deformability may be the key mechanism in this relationship. Therefore, this study has been performed to determine if there is a relationship between the pineal gland and melatonin and red cell deformability. Twenty-eight rats underwent pinealectomy, pinealectomy plus melatonin administration (200 mg/kg), or no treatment (n=7 in each group). Erythrocyte deformability was determined using the filtration technique. The results are reported in mean (+/-SD) seconds: control: 1.45+/-0.44; pinealectomy (A): 1.55+/-0.16; pinealectomy (B): 1.34+/-0.26 and pinealectomy and melatonin: 2.56+/-0.69. Pinealectomy by itself did not cause any statistically significant change in erythrocyte deformability but the addition of melatonin significantly decreased it. These results suggest a relationship between melatonin and erythrocyte deformability. Further investigations may uncover the causes of the circadian rhythm of stroke and MI, which may help improve chronobiological therapies.     

What does the spleen see?

In this issue of Blood, Safeukui et al have come to grips with an important issue in red blood cell (RBC) biology.1 Their study deals not only with the mechanism of RBC removal in diseases like hereditary spherocytosis (HS) and autoimmune hemolytic anemia, but also with RBC senescence.     

Nickel-induced allergy and contact dermatitis: does it induce autoimmunity and cutaneous sclerosis? An experimental study in Brown Norway rats

Nickel sensitization is a growing problem and the most common cause of allergic contact dermatitis. The aim of this study was to investigate whether nickel chloride can induce autoimmunity and cutaneous sclerosis in immunosensitive rats. Nickel chloride, in a dose of 4.5 mg in 0.2 ml NS, was administered by the oral and subcutaneous routes to 20 Brown Norway rats. Autoantibodies (ANA, anti-RNP, anti-SCL70 and anti-centromere) were measured and compared in pre- and post-challenge serum samples. Histological studies were also performed in skin biopsies obtained from six positively responding rats and compared with an equal number of control rats at the 14th week post-challenge. Serum ANA was high in a significant number of rats in both the oral (P < 0.005) and subcutaneously nickel-treated groups (P = 0.02), while the anti-SCL70 was high in a significant number of rats in only the orally nickel-treated group (P = 0.04). Histologically, subcutaneous and oral nickel-treated groups showed sclerodermic features of the skin (P = 0.22, P = 0.5), respectively. It may be concluded that nickel chloride can induce scleroderma-related autoantibodies and cutaneous sclerosis. More prolonged duration of exposure is probably associated with greater risk. This is the first study showing the potential risk of nickel in triggering the development of cutaneous sclerosis in susceptible hosts.     

Coagulation and metastasis: what does the experimental literature tell us?

Inhibition of coagulation greatly limits cancer metastasis in many experimental models. Cancer cells trigger coagulation, through expression of tissue factor or P‐selectin ligands that have correlated with worse prognosis in human clinical studies. Cancer cells also affect coagulation through expression of thrombin and release of microparticles that augment coagulation. In the cancer‐bearing host, coagulation facilitates tumour progression through release of platelet granule contents, inhibition of Natural Killer cells and recruitment of macrophages. We are revisiting this literature in the light of recent studies in which treatment of clinical cohorts with anticoagulant drugs led to diminished metastasis.     

Management of renal artery stenosis: What does the experimental evidence tell us?

Optimal management of patients with renal artery stenosis(RAS) is a subject of considerable controversy. There is incontrovertible evidence that renal artery stenosis has profound effects on the heart and cardiovascular system in addition to the kidney. Recent evidence indicates that restoration of blood flow alone does not improve renal or cardiovascular outcomes in patients with renal artery stenosis. A number of human and experimental studies have documented the clinical, hemodynamic, and histopathologic features in renal artery stenosis. New approaches to the treatment of renovascular hypertension due to RAS depend on better understanding of basic mechanisms underlying the development of chronic renal disease in these patients. Several groups have employed the two kidney one clip model of renovascular hypertension to define basic signaling mechanisms responsible for the development of chronic renal disease. Recent studies have underscored the importance of inflammation in the development and progression of renal damage in renal artery stenosis. In particular, interactions between the renin-angiotensin system, oxidative stress, and inflammation appear to play a critical role in this process. In this overview, results of recent studies to define basic pathways responsible for renal disease progression will be highlighted. These studies may provide the rationale for novel therapeutic approaches to treat patients with renovascular hypertension.     

What does sustainability mean in the HIV and AIDS response?

Immense progress has been made in the fight against HIV and AIDS. Achieving and exceeding the AIDS targets for the Millennium Development Goals (MDGs) was accomplished, in large part, due to an unprecedented financial investment from the international community. Following an $800 million dip in donor disbursements in 2010, the discourse has since shifted to the need for greater sustainability of funding. But what does sustainability mean? Current efforts focus heavily on fiscal imperatives such as increasing domestic funding. This is important – needs are increasing at a faster rate than donor funding, especially with increased treatment coverage. The problem is that measures of financial sustainability tell very little about the actual sustainability of specific programmes, disease trajectories or enabling environments.

Recognising that current definitions of sustainability lack clarity and depth, we offer a new six-tenet conceptualisation of what sustainability means in the HIV and AIDS response: (1) financial, (2) epidemiological, (3) political, (4) structural, (5) programmatic, and (6) human rights. Based on these, we examine examples of donor transitions for their approach to sustainability, including PEPFAR in South Africa, the Global Fund in Eastern Europe, and the Bill and Melinda Gates Foundation in India (Avahan). We conclude that sustainability must be understood within a broader framework beyond funding stability. We also recommend that certain interventions, such as programming for key populations, may have to continue to receive external support even if affected countries can afford to pay.     

Can dantrolene protect spinal cord against ischemia/reperfusion injury? An experimental study

BACKGROUND: The aim of this experimental study was to investigate the possible protective effect of dantrolene on neuronal injury induced by aortic ischemia/reperfusion (I/R). METHODS: Nineteen rabbits were divided into three groups: sham (group 1, n = 5, no I/R), control (group 2, n = 7, only I/R) and dantrolene (group 3, n = 7, dantrolene + I/R). Abdominal aortic occlusion between the renal arteries and iliac bifurcations was carried out for 30 min. The spinal cord functions of the subjects were assessed using the Tarlov Scale. Blood and cord tissue samples were taken for biochemical and histopathological evaluation. RESULTS: Tarlov scores in group 3 were significantly higher than in group 2 ( P < 0.05). In group 3, the MDA levels of the spinal cord decreased significantly compared to those of group 2 ( P < 0.05). In rabbits with I/R (group 2), the GSH levels of the spinal cord decreased significantly compared to those of group 1 ( P < 0.01), but dantrolene pretreatment significantly prevented a decrease in GSH levels. Histopathological examination showed that group 3 had less vascular proliferation, hemorrhage, edema and neuron loss than group 2. CONCLUSIONS: It was concluded that dantrolene applied after ischemia might help protect the spinal cord against ischemia/reperfusion injury.     

Does a fibrin-collagen patch support early anastomotic healing in the colon? An experimental study

Background The aim of this study was to evaluate the effect of absorbable fibrin-collagen patch (FCP) during early colonic anastomotic healing in rats. Methods Prepubertal Wistar albino rats were randomly divided into 6 groups of 6 rats each. Colon was transected and then anastomosed with sutures (Group A), sutures+FCP (TachoComb; Nycomed, Austria) (Group AT) or only FCP (Group T). Rats were sacrificed either 3 or 7 days after the anastomosis. Anastomoses were evaluated for perianastomotic adhesion formation, bursting pressures and histological features. Results Perianastomotic adhesion formation was significant in Groups AT and T. Bursting pressures were in higher group AT than in Group A on postoperative day 3 and lower on day 7 (p<0.05). Histological examinations revealed an increase in inflammatory cells in Group T on day 3 and decreased wound healing in Group AT when compared to Group A on day 7 (p<0.05). Conclusions In the early period of anastomotic healing, FCP supports anastomotic integrity. However, it also causes an inflammatory reaction which may increase the time necessary for healing process. Thus, the use of this biomaterial should be preferred in only selective clinical cases with a careful follow-up. This study was presented as an oral presentation at the VI^th European Congress of Paediatric Surgery in Gdansk, Poland, 25–28 May 2005.     

Is dietary erucic acid hepatotoxic in pregnancy? An experimental study in rats and hamsters

The hypothesis that dietary erucic acid may contribute to the pathogenesis of intrahepatic cholestasis of pregnancy has been examined in pregnant rats and hamsters after prolonged feeding of diets containing 25% rapeseed oil rich in erucic acid (40% of fatty acids) or corn oil, without erucic acid. Both dietary oils were well tolerated, although weight gain was 17% to 20% less in animals receiving rapeseed oil. Rats and hamsters were studied on the last day of pregnancy and compared with age- and diet-matched nonpregnant animals. Histological examination showed no major morphologic abnormalities in liver, heart, kidneys, and adrenals. Similar microscopic deposits of fat were found in the livers and hearts of pregnant hamsters of both dietary groups. Chromatographic analysis of fatty acids in liver, heart, and kidney homogenates of hamsters and in isolated rat liver cells reflected the fatty acid composition of the dietary oils: oleic (18:1) and linoleic (18:2) acids were among the predominant fatty acids. Erucic acid was found in a higher proportion in the heart (14% by weight of total fatty acids) than in the liver (3%) and kidneys (3%) of animals fed rapeseed oil. Bile flow and biliary lipid composition was similar in rats and hamsters fed rapeseed or corn oil. Bile flow tended to be less in pregnant than in nonpregnant animals. Pregnant hamsters fed rapeseed oil tended to have the lowest bile flow. The lithogenic index of bile was slightly decreased in pregnant rats and increased in pregnant hamsters, although these proportional changes were similar for both diets. In all circumstances the lithogenic index remained below a value of 1. Biliary excretion of sulfobromophthalein (BSP) and maximal transport capacity of BSP into bile (BSP Tm) were similar in rats fed rapeseed or corn oil diets. In conclusion, no morphologic or hepatic functional abnormalities attributable to the diet could be detected in animals fed rapeseed oil with a high content of erucic acid, whereas pregnancy induced changes in bile secretion in rats and hamsters, irrespective of the diet administered. These observations are still insufficient to reject the possibility that rapeseed oil rich in erucic acid could be involved in the pathogenesis of intrahepatic cholestasis of pregnancy because dietary erucic acid could interact with a genetic metabolic predisposition to induce a disease that seems to be specific to humans.     

Functional gastrointestinal disorders and gut-brain axis: What does the future hold?

Despite their high prevalence, lack of understanding of the exact pathophysiology of the functional gastrointestinal disorders has restricted us to symptomatic diagnostic tools and therapies. Complex mechanisms underlying the disturbances in the bidirectional communication between the gastrointestinal tract and the brain have a vital role in the pathogenesis and are key to our understanding of the disease phenomenon. Although we have come a long way in our understanding of these complex disorders with the help of studies on animals especially rodents, there need to be more studies in humans, especially to identify the therapeutic targets. This review study looks at the anatomical features of the gut-brain axis in order to discuss the different factors and underlying molecular mechanisms that may have a role in the pathogenesis of functional gastrointestinal disorders. These molecules and their receptors can be targeted in future for further studies and possible therapeutic interventions. The article also discusses the potential role of artificial intelligence and machine learning and its possible role in our understanding of these scientifically challenging disorders.     

COVID-19 and diabetes: What does the clinician need to know?

COVID-19 and diabetes are currently two global pandemics. Epidemiological studies indicate that diabetes is the second most common comorbidity in COVID-19. This review aims to summarize currently available data about prevalence, possible pathophysiological mechanisms and management of patients with diabetes and COVID-19.     

What does Cruzan mean to the practicing physician?

The United States Supreme Court's recent decision in the Cruzan case declared that the states have broad powers to formulate their own rules in "right to die" cases. The Court held that competent adults have a constitutionally protected "liberty interest" that allows them to accept or refuse medical treatments. Since liberty interests are subject to rational state regulation, the narrow holding in Cruzan affirmed Missouri's authority to require a "clear and convincing" evidence standard to determine a patient's wishes before life-sustaining treatment could be withdrawn from a formerly competent adult now in a persistent vegetative state. For practicing physicians, some of the implications of Cruzan are as follows: (1) For competent adult patients, physicians should respect patient wishes regarding life-sustaining treatment. (2) Physicians also should discuss with competent patients their wishes for life-sustaining treatment at a future time, when a patient may no longer be able to participate in such decisions. (3) Physicians should record these wishes in a legally acceptable instrument that addresses two aspects of care that may arise in the future if the patient becomes incompetent. What would the patient want done? Who would the patient wish to designate as a surrogate or proxy? (4) For patients who are now incompetent, but for whom decisions must be made about life-sustaining treatment, physicians should focus on the previously expressed wishes of the patient rather than on the patient's current quality of life or on the wishes of the patient's family.     

An experimental study on the immunity to Ascaris suum in Guinea pigs.

The immunological activity induced in guinea pigs by two Ascaris suum antigensand the reaction of the immunized guinea pigs to A. suum infection were investigated.The animals were immunized with soluble antigen of whole adult worm intramuscularly