Subclinical endometritis in estrual buffaloes: diagnosis, prevalence and impact on reproductive performance.

The study evaluated the reliability of polymorphonuclear (PMN) cell count in endometrial cytology by cytobrush technique as a diagnostic for subclinical endometritis (SCE) at the time of estrus and its relationship with bacterial presence and fertility in buffaloes. Healthy pluriparous buffaloes (n = 115) were subjected to endometrial sampling by cytobrush technique (for cytology and bacterial isolation) and ultrasonography of genitalia prior to insemination at the time of spontaneous estrus. Buffaloes were inseminated at the same estrus and were confirmed for pregnancy by ultrasonography at day 40 post-insemination. Growth of aerobic bacteria was recorded in 26.1% (30/115) of estrual buffaloes. Bacteria of eight distinct genera (Staphylococcus spp., Bacillus spp., Proteus spp., Escherichia coli, Klebsiella spp., Streptococcus spp., Pseudomonas spp. and T. pyogenes) were isolated. Presence of bacterial infection was considered as the standard, against which PMN threshold for SCE was calculated by receiver operator curve (ROC). The PMN count of ≥ 5% with good sensitivity (66.7, 95% CI 50.9-81.4) and specificity (87.0%, 95% CI 78.0-94.6) with an overall high diagnostic accuracy (81.7%) for predicting SCE was obtained. Based on calculated PMN threshold, buffaloes were divided into subclinical endometritic (SCE; ≥ 5% PMNs) and control (< 5% PMNs) groups. Thirty-one buffaloes (27.0%, 31/115) had ≥ 5% PMNs in the endometrial cytology at estrus. Ultrasonographic evaluation showed that size of largest follicle, endometrial thickness, and uterine horn diameter did not differ significantly (P > 0.05) between the two groups. Significantly, lower conception rate (22.58 vs 36.90%, P < 0.05) for first artificial inseminations (AIs) and significantly higher number of AIs per pregnancy (2.81 ± 0.27 vs 1.75 ± 0.15, P < 0.05) were recorded in SCE compared to control group. The results indicated that cytobrush based endometrial cytology with 5% PMN cut-off value has a good accuracy for predicting subclinical endometritis at estrus in buffaloes.

A mixed anti-inflammatory and pro-inflammatory response associated with a high dose of corticosteroids.

OBJECTIVE: Hydrocortisone, at a low dose (100 mg), induces an anti-inflammatory response including inducing IkBα and suppressing intranuclear NFκB and AP-1 binding and the expression of pro-inflammatory mediators like MMPs. We have now investigated the effect of a high dose of hydrocortisone (300mg=60 mg prednisolone) on NFκB binding and the expression of TLRs, the mediators of TLR signal transduction, MyD88 and TRIF and HMG-B1. DESIGN AND SUBJECTS: A 300mg of hydrocortisone or saline was injected intravenously in ten normal subjects during 2 separate visits, in a randomized crossover study. Blood samples were obtained at 0, 1, 4, 6 and 24h after the injection and mononuclear cells (MNC) were prepared. RESULTS: There was a significant increase in glucose (from 92±4 to 116±6 mg/dl), insulin (from 4.5±0.7 to 5.3±0.8 mU/ml) and FFA concentrations (from 0.38±0.1 to 0.80±0.15mM) following the administration of hydrocortisone compared to placebo treatment. While NFκB binding and the mRNA expression of MyD88, TRIF, chemokines and chemokine receptors were suppressed significantly in MNC, there was a paradoxical increase in the mRNA expression of TLR 2, 5 and 9 and HMG-B1 was increased by 103±24%, 107±19%, 56±13% and 58±12% above the baseline, respectively in the MNC. Plasma concentrations of HMG-B1 and MMP-9 increased by 37±12% and 125±22%, respectively, while TNF-α concentrations fell by 27±9%. CONCLUSION: While this high dose of hydrocortisone exerts a powerful anti-inflammatory effect, it also exerts certain proinflammatory effects mainly on TLRs expression. The known pro-inflammatory effects of glucose and FFAs may have contributed to these effects. These paradoxical pro-inflammatory effects may account for the inability of these drugs to show benefit in clinical trials of septicemia and other severe pro-inflammatory states and might contribute to some of the side effects of corticosteroids use.

Uterine blood flow during various stages of pregnancy in dairy buffaloes using transrectal Doppler ultrasonography.

Reference data to assess function and perfusion of uteroplacental tissues by assessment of uterine blood flow parameters is not available in buffaloes. The objective of the present study was to assess and quantify blood flow parameters at various stages of gestation. A total of 54 Murrah buffaloes, six animals at every month of gestation, from two months to ten months, were subjected to transrectal Doppler ultrasonography to assess uterine blood flow in both the middle uterine arteries. Resistance and pulsatility indices, velocity and volume of blood flow, diameter of the artery and notch signal were measured for different waveforms. The resistance index value was positively correlated with pulsatility index (r=0.94, P<0.05) but negatively correlated with all other parameters for both arteries, ipsilateral and contralateral to the fetus. With a significant advancement of pregnancy, there was reduction in resistance index with a significant increase in velocity, volume of blood flow and diameter in both arteries. There was a significant increase in the volume and velocity of blood flow (P<0.05) during the last trimester with increased growth demands of the fetus. The notch signal disappeared by 20-24 weeks. Thus, transrectal Doppler ultrasongraphy proved to be a useful non-invasive method to assess the uterine blood flow during pregnancy in buffaloes. This could be a valuable tool to ascertain hemodynamic changes in complicated pregnancy (e.g. abnormalities in uterine blood flow/placenta/fetus) and its extent of deviation from normal.

Hypogonadotrophic hypogonadism in type 2 diabetes.

Recent work shows a high prevalence of low testosterone and inappropriately low luteinizing hormone (LH) and follicle stimulating hormone (FSH) concentrations in type 2 diabetes. This syndrome of hypogonadotrophic hypogonadism (HH) is associated with obesity in patients with type 2 diabetes. However, the duration of diabetes or HbA1c are not related to HH. Furthermore, recent data show that HH is not associated with type 1 diabetes. C-reactive protein concentrations have been shown to be elevated in patients with HH and are inversely related to plasma testosterone concentrations. This inverse relationship between plasma free testosterone and C- reactive protein concentrations in patients with type 2 diabetes suggests that inflammation may play an important role in the pathogenesis of this syndrome. This is of interest since inflammatory mechanisms may have a cardinal role in the pathogenesis of insulin resistance. It is also relevant that in the mouse, deletion of the insulin receptor in neurons leads to HH in addition to a state of systemic insulin resistance. It has also been shown that insulin facilitates the secretion of gonadotrophin releasing hormone (GnRH) from neuronal cell cultures. Thus, HH may be the result of insulin resistance at the level of the GnRH secreting neuron. Low testosterone concentrations are also related to an increase in total and regional adiposity. This review discusses these issues and attempts to make the syndrome relevant as a clinical entity. Clinical trials are required to determine whether testosterone replacement alleviates insulin resistance and inflammation. In addition, low testosterone levels are associated with an increase in cardiovascular events. Testosterone therapy may therefore, reduce cardiovascular risk. This important aspect requires further investigation.

Angiotensin II and inflammation: the effect of angiotensin-converting enzyme inhibition and angiotensin II receptor blockade.

Angiotensin II (Ang II) increases adhesion molecules, cytokines and chemokines and exerts a proinflammatory effect on leucocytes, endothelial cells and vascular smooth muscle cells. Acting via the type 1 receptor, Ang II initiates an inflammatory cascade of reduced nicotinamide-adenine dinucleotide phosphate oxidase, reactive oxygen species (ROS) and nuclear factor-kappaB, which mediates transcription and gene expression and increases adhesion molecules and chemokines. An excess of ROS decreases nitric oxide bioavailability, causes endothelial dysfunction, and promotes atherosclerosis. Moreover, Ang II interrupts the anti-inflammatory effects of insulin. Together, these effects promote a prothrombotic state as well as plaque rupture. Ang II receptor blockers suppress mediators of inflammation, including ROS and C-reactive protein, and they increase expression of inhibitory kappaB (an inhibitor of nuclear factor-kappaB). These anti-inflammatory and antioxidative effects, which are probably due in part to unopposed stimulation of the Ang II type 2 receptor, may be beneficial in acute coronary syndromes and may also contribute to the prevention of type II diabetes mellitus, as insulin resistance is mediated by inflammatory processes.

Vulnerable plaques, inflammation and newer imaging modalities.

Currently, inflammation is considered to be the central player in the pathogenesis of atherosclerosis. It leads to the formation of multiple plaques in the arterial beds including coronary vasculature. Recent studies using the latest imaging techniques have shown that in patients with acute coronary syndromes (ACS) multiple plaques are ruptured and have thrombus formation on them. Various factors make these plaques unstable, these include structural components of plaque like thin fibrous cap, high lipid content of the plaque core and inflammation, both localized and generalized. It has been shown that most of the ACS are caused by plaques causing non-critical stenosis as seen on traditional X-ray angiography. Also, the phenomenon of remodelling makes angiography a poor technique for plaque visualization. Hence newer modalities are required to identify these "vulnerable plaques". Intravascular ultrasound (IVUS), thermography and Magnetic Resonance Imaging (MRI) are a few such promising techniques. Here we review the invasive and non-invasive modalities that can be helpful in the identification of these plaques before they become unstable and cause ACS, and also the available therapies to stabilize these plaques.

Brain natriuretic peptide in diagnosis and treatment of heart failure.

Currently we are in the midst of a chronic disease epidemic of congestive heart failure (CHF) worldwide. This epidemic is marked by a rapid rise in prevalent cases over the past decade that is due in part to the aging population and improved survival in patients with other cardiovascular conditions. At present there are 5 million Americans with congestive heart failure, with nearly 500000 new cases every year. To provide cost-effective treatment for patients with congestive heart failure, rapid and accurate differentiation of congestive heart failure from other causes of dyspnea must be accomplished. Although echocardiography is considered the gold standard for the detection of left ventricular dysfunction, it is expensive, is not always easily accessible, and may not always reflect an acute condition. B-type natriuretic peptide (BNP) is a cardiac neurohormone specifically secreted from the cardiac ventricles as a response to ventricular volume expansion, pressure overload, and resultant increased wall tension. BNP can be used in the diagnosis of CHF. However, the present American College of Cardiology/American Heart Association practice guidelines (2001) for the evaluation and management of CHF state that the role of blood BNP in the identification of patients with CHF remains to be fully clarified. We have discussed the role of BNP in the diagnosis and management of CHF.

Cardiac resynchronization therapy in heart failure: recent advances and new insights.

Newer non-pharmacological therapies for heart failure are being evaluated for patients of congestive heart failure (CHF). Mechanical support with left ventricular assist devices and heart transplantation are reserved for the minority of patients who have severely decompensated heart failure. Despite these therapeutic advances, it is generally accepted that current therapies do not adequately address the clinical need of patients with heart failure, and additional strategies are being developed. Cardiac resynchronization therapy (CRT) is a new modality that involves synchronization of ventricular contraction and has shown a lot of promise in managing symptomatic patients of CHF who are on optimal medical therapy and have interventricular conduction delay (IVCD). It has improved exercise tolerance and NYHA functional class in such patients in sinus rhythm and a recent meta-analysis has also shown mortality benefits in CHF. Recently benefits of CRT have also been observed in CHF patients who do not have wide QRS complexes on electrocardiogram (EKG). It has also been shown to benefit drug refractory angina in CHF. Recent studies have also focused on the combined use of CRT and implantable cardioverter defibrillator (ICD) and it has shown encouraging results. Our aim in this descriptive review is to define practice guidelines and to improve clinicians' knowledge of the available published clinical evidence, concentrating on few randomized controlled trials.