Exploring a new frontier in cardiac diagnosis: ECG analysis enhanced by machine learning and parametric quartic spline modeling.

The heart's study holds paramount importance in human physiology, driving valuable research in cardiovascular health. However, assessing Electrocardiogram (ECG) analysis techniques poses challenges due to noise and artifacts in authentic recordings. The advent of machine learning systems for automated diagnosis has heightened the demand for extensive data, yet accessing medical data is hindered by privacy concerns. Consequently, generating artificial ECG signals faithful to real ones is a formidable task in biomedical signal processing. This paper introduces a method for ECG signal modeling using parametric quartic splines and generating a new dataset based on the modeled signals. Additionally, it explores ECG classification using three machine learning techniques facilitated by Orange software, addressing both normal and abnormal sinus rhythms. The classification enables early detection and prediction of heart-related ailments, facilitating timely clinical interventions and improving patient outcomes. The assessment of synthetic signal quality is conducted through power spectrum analysis and cross-correlation analysis, power spectrum analysis of both real and synthetic ECG waves provides a quantitative assessment of their frequency content, aiding in the validation and evaluation of synthetic ECG signal generation techniques. Cross-correlation analysis revealing a robust correlation coefficient of 0.974 and precise alignment with a negligible time lag of 0.000 s between the synthetic and real ECG signals. Overall, the adoption of quartic spline interpolation in ECG modeling enhances the precision, smoothness, and fidelity of signal representation, thereby improving the effectiveness of diagnostic and analytical tasks in cardiology. Three prominent machine learning algorithms, namely Decision Tree, Logistic Regression, and Gradient Boosting, effectively classify the modeled ECG signals with classification accuracies of 0.98620, 0.98965, and 0.99137, respectively. Notably, all models exhibit robust performance, characterized by high AUC values and classification accuracy. While Gradient Boosting and Logistic Regression demonstrate marginally superior performance compared to the Decision Tree model across most metrics, all models showcase commendable efficacy in ECG signal classification. The study underscores the significance of accurate ECG modeling in health sciences and biomedical technology, offering enhanced accuracy and flexibility for improved cardiovascular health understanding and diagnostic tools.

Phage for drug delivery vehicles.

Viruses being the natural carriers of gene have been widely used as drug delivery systems. However, the commonly used eukaryotic viruses such as adenoviruses, retroviruses, and lentiviruses, besides efficiently targeting the cells, can also stimulate immunological response or disrupt tumour suppressor genes leading to cancer. Consequently, there has been an increase interest in the scientific fraternity towards exploring other alternatives, which are safer and equally efficient for drug delivery. Bacteriophages, in this context have been at the forefront as an efficient, reliable, and safer choice. Novel phage dependent technologies led the foundation of peptide libraries and provides way to recognising abilities and targeting of specific ligands. Hybridisation of phage with inorganic complexes could be an appropriate strategy for the construction of carrying bioinorganic carriers. In this chapter, we have tried to cover major advances in the phage species that can be used as drug delivery vehicles.

Chain length effect of spiro-ring N-alkylation on photophysical signalling parameters in Fe(III) selective rhodamine probes.

Manifestation of photophysical signalling parameters in rhodamine derivatives exhibiting complexation induced spiro-ring opening is crucial for the realization of selective metal ion detection at trace levels. Substitution of various functional groups, such as alkylation to the core architecture, modulates the physico-chemical properties of such molecular probes. Despite a few studies, relationships between the extent of photophysical signal modulations and the chain lengths of n-alkyl substituents are still elusive. In this investigation, a few molecular probes based on the rhodamine B (1-5) and rhodamine 6G (6-10) platform were synthesized by their derivatization with n-alkyl substituents of varying chain lengths at the amino-donor of their spiro-ring end, which exhibited Fe(III)-selective absorption and fluorescence 'off-on' signal transduction along with colorization of solution. The Fe(III)-selectivity in these probes remained the same despite their structural distinctions through varied n-alkyl chain lengths of the substituents; however, the quantifiable signalling parameters such as spectroscopic enhancement factors, sensitivity, the kinetics of spiro-ring opening and effectiveness of probe-Fe(III) interactions were analyzed. These parameters were also correlated in terms of the influence of different chain lengths of n-alkyl substituents that efficiently contributed to their inter-componential interactive stereo-electronic environment.

Current status and applications of genus Geobacillus in the production of industrially important products-a review.

The genus Geobacillus is one of the most important genera which mainly comprises gram-positive thermophilic bacterial strains including obligate aerobes, denitrifiers and facultative anaerobes having capability of endospore formation as well. The genus Geobacillus is widely distributed in nature and mostly abundant in extreme locations such as cool soils, hot springs, hydrothermal vents, marine trenches, hay composts and dairy plants. Due to plasticity towards environmental adaptation, the Geobacillus sp. shows remarkable genome diversification and acquired many beneficial properties, which facilitates their exploitation for many biotechnological applications. Many thermophiles are of biotechnological importance and having considerable interest in commercial applications for the production of industrially important products. Recently, due to catabolic versatility especially in the degradation of hemicellulose and starch containing agricultural waste and rapid growth rates, these microorganisms show potential for the production of biofuels, thermostable enzymes and bioremediation. This review mainly summarizes the status of Geobacillus sp. including its notable properties, biotechnological studies and its potential application in the production of industrially important products.

A rapid method for solubilization of chimeric human interferon regulatory factor-1 (IRF-1) protein in Escherichia coli.

Interferon regulatory factor-1 (IRF-1) is a vertebrate transcription factor that plays significant roles in cell cycle regulation, anti-viral response, tumor suppression and immune response. High-level expression of recombinant IRF-1 at 37 °C leads to the formation of insoluble aggregates (insoluble fraction) in Escherichia coli (E. coli), which usually devoid of biological activity. In this study, we use chemical additives such as mannitol, proline, L-arginine and CTAB (cetyl trimethly ammonium bromide) at the recommended concentration during cell lysis to aid in solubility at 37 °C. The use of additives resulted in the increased solubility of the recombinant glutathione S-transferase-linked human IRF-1, with L-arginine being most effective. Here, we developed an efficient process for the manufacturing of soluble IRF-1 with the aid of minimizing the formation of degradation products and optimizing protein purification conditions. This result was further confirmed by western blot with anti-GST and anti-IRF-1 polyclonal antibodies. The functionality of GST-huIRF-1 was attained by elerophoretic mobility shift assay study as a clear band shifting showed with virus response element-Interferon beta (VRE-IFNß) promoter region. Taken together, the biological activity of purified GST-huIRF-1 was also optimized and confirmed by supershift assay concluded that GST-huIRF-1 interacts with the VRE motif of IFNß promoter that reflected to require for IFNß gene regulation. We describe a straightforward approach for the production of absolutely soluble and biologically active IRF-1 in E. coli. This method can be further used for the study of other recombinant proteins and this study will pave way for the analysis of IRF-1 function in vitro.

Reduced-sodium cheeses: Implications of reducing sodium chloride on cheese quality and safety.

Sodium chloride (NaCl) universally well-known as table salt is an ancient food additive, which is broadly used to increase the storage stability and the palatability of foods. Though, in recent decades, use of table salt in foods is a major concern among the health agencies of the world owing to ill effects of sodium (Na) that are mostly linked to hypertension and cardiovascular diseases. As a result, food scientists are working to decrease the sodium content in food either by decreasing the rate of NaCl addition or by partial or full replacement of NaCl with other suitable salts like potassium chloride (KCl), calcium chloride (CaCl2 ), or magnesium chloride (MgCl2 ). However, in cheese, salt reduction is difficult to accomplish owing to its multifaceted role in cheese making. Considering the significant contribution in dietary salt intake (DSI) from cheese, researchers across the globe are exploring various technical interventions to develop reduced-sodium cheeses (RSCs) without jeopardizing the quality and safety of cheeses. Thus, the purpose of this study is to provide an insight of NaCl reduction on sensory, physicochemical, and technofunctional attributes of RSCs with an aim to explore various strategies for salt reduction without affecting the cheese quality and safety. The relationship between salt reduction and survival of pathogenic and spoilage-causing microorganisms and growth of RSCs microflora is also discussed. Based on the understanding of conceptual and applied information on the complex changes that occur in the development of RSCs, the quality and safety of RSCs can be accomplished effectively in order to reduce the DSI from cheese.

Role of TRP Channels in Shaping the Gut Microbiome.

Transient receptor potential (TRP) channel family proteins are sensors for pain, which sense a variety of thermal and noxious chemicals. Sensory neurons innervating the gut abundantly express TRPA1 and TRPV1 channels and are in close proximity of gut microbes. Emerging evidence indicates a bi-directional gut-brain cross-talk in several entero-neuronal pathologies; however, the direct evidence of TRP channels interacting with gut microbial populations is lacking. Herein, we examine whether and how the knockout (KO) of TRPA1 and TRPV1 channels individually or combined TRPA1/V1 double-knockout (dKO) impacts the gut microbiome in mice. We detect distinct microbiome clusters among the three KO mouse models versus wild-type (WT) mice. All three TRP-KO models have reduced microbial diversity, harbor higher abundance of Bacteroidetes, and a reduced proportion of Firmicutes. Specifically distinct arrays in the KO models are determined mainly by S24-7, Bacteroidaceae, Clostridiales, Prevotellaceae, Helicobacteriaceae, Rikenellaceae, and Ruminococcaceae. A1KO mice have lower Prevotella, Desulfovibrio, Bacteroides, Helicobacter and higher Rikenellaceae and Tenericutes; V1KO mice demonstrate higher Ruminococcaceae, Lachnospiraceae, Ruminococcus, Desulfovibrio and Mucispirillum; and A1V1dKO mice exhibit higher Bacteroidetes, Bacteroides and S24-7 and lower Firmicutes, Ruminococcaceae, Oscillospira, Lactobacillus and Sutterella abundance. Furthermore, the abundance of taxa involved in biosynthesis of lipids and primary and secondary bile acids is higher while that of fatty acid biosynthesis-associated taxa is lower in all KO groups. To our knowledge, this is the first study demonstrating distinct gut microbiome signatures in TRPA1, V1 and dKO models and should facilitate prospective studies exploring novel diagnostic/ therapeutic modalities regarding the pathophysiology of TRP channel proteins.

Effect of n-alkyl substitution on Cu(ii)-selective chemosensing of rhodamine B derivatives.

Rhodamine B hydrazide-based molecular probes (1-10) were synthesized by derivatization with n-alkyl chains of different lengths at the hydrazide amino end. These probes exhibited selective absorption (A∼557) and fluorescence (I∼580) 'off-on' signal transduction along with a colourless → magenta colour transition in the presence of Cu(ii) ions among all the competitive metal ions investigated. The effective coordination of these probes to Cu(ii) ions under the investigated environment forming [Cu·L]2+ (L = 1-5) and [Cu·L2]2+ (L = 6-10) complexes led to their spiro-ring opening, which in turn was expressed through signatory spectral peaks of ring-opened rhodamine. All these probes exhibited Cu(ii) selectivity in signalling despite structural modifications to the core receptor unit through variation of the nature of the alkyl substituents. However, the sensitivity of the signalling and kinetics of the spiro-ring opening varied and could be correlated with the number of carbon atoms present in the n-alkyl substituents. Structural elucidation with X-ray diffraction and X-ray photoemission spectroscopic analyses provided further insight into the structure-function correlation in their Cu(ii) complexes. These probes with Cu(ii) coordination showed selectivity in signalling, high complexation affinity (log Ka = 4.8-8.8), high sensitivity (LOD = 4.1-80 nM), fast response time (rate = 0.0017-0.0159 s-1) and reversibility with counter anions, which ascertained their potential utility as chemosensors for Cu(ii) ion detection.

Possible bioremediation of arsenic toxicity by isolating indigenous bacteria from the middle Gangetic plain of Bihar, India.

In middle Gangetic plain, high arsenic concentration is present in water, which causes a significant health risk. Total 48 morphologically distinct arsenite resistant bacteria were isolated from middle Gangetic plain. The minimum inhibitory concentration (MIC) values of arsenite varied widely in the range 1-15 mM of the isolates. On the basis of their MIC, two isolates, AK1 (KY569423) and AK9 (KY569424) were selected. The analysis of the 16S rRNA gene sequence of selected isolates revealed that they are belong to the genus Pseudomonas. The AgNO3 test based microplate method revealed that isolates, AK1 and AK9, have potential in transformation of arsenic species. Further, the presence of aoxR, aoxB and aoxC genes in the both isolated strain AK1 and AK9 was confirmed, which play an important role in arsenic bioremediation by arsenite oxidation. Isolated strains also showed heavy metal resistance against Cr(IV), Ni(II), Co(II), Pb(II), Cu(II), Hg(II), Ag(I) and Cd(II).

Experimental Protocol for Cecal Ligation and Puncture Model of Polymicrobial Sepsis and Assessment of Vascular Functions in Mice.

Sepsis is the systemic inflammatory response syndrome that occurs during infection and is exacerbated by the inappropriate immune response encountered by the affected individual. Despite extensive research, sepsis in humans is one of the biggest challenges for clinicians. The high mortality rate in sepsis is primarily due to hypoperfusion-induced multiorgan dysfunctions , resulting from a marked decrease in peripheral resistance. Vascular dysfunctions are further aggravated by sepsis-induced impairment in myocardial contractility. Circulatory failure in sepsis is characterized by refractory hypotension and vascular hyporeactivity (vasoplegia) to clinically used vasoconstrictors. To investigate the complex pathophysiology of sepsis and its associated multiple organ dysfunction, several animal models have been developed. However, cecal ligation and puncture (CLP) model of murine sepsis is still considered as 'gold standard' in sepsis research. In this protocol we have described the standard surgical procedure to induce polymicrobial sepsis by cecal ligation and puncture. Further, we have described the protocol to study the molecular mechanisms underlying vascular dysfunctions in sepsis.

Microencapsulation of reuterin to enhance long-term efficacy against food-borne pathogen Listeria monocytogenes.

The aim of this study was to microencapsulate the reuterin produced by Lactobacillus reuteri BPL-36 strain for its long-term efficacy against food-borne pathogen Listeria monocytogenes. Lactobacillus reuteri BPL-36 strain previously isolated from a human infant fecal sample in lab was selected for the present study based on its ability to produce reuterin. The organism displayed a broad-spectrum antimicrobial activity. Reuterin concentration of 89.63 mM was obtained in the MRS-glycerol medium after 16 h incubation at 37 °C. The reuterin concentration required to inhibit the growth of Pseudomonas aeruginosa, Escherichia coli O157: H7, Salmonella typhi, Staphylococcus aureus, and Listeria monocytogenes was found to be 1.0, 2.0, 2.0, 4.0, and 10.0 AU/mL, respectively. Microencapsulation of reuterin to enhance long-term efficacy against food-borne pathogens was done. Results in this study indicated that the release characteristics of reuterin from the encapsulated particles were pH dependent. The release characteristics were unaffected by the storage of encapsulated reuterin at 4 °C for 2 weeks. The anti-listerial efficacy of the encapsulated reuterin was tested against L. monocytogenes in the BHI medium adjusted to pH 5.0 with a reuterin content equivalent to 16 mM, similar to un-encapsulated (free) reuterin. Encapsulated reuterin demonstrated enhanced efficacy against L. monocytogenes for longer duration of time when compared with un-encapsulated (free) reuterin. The present work demonstrated a novel antimicrobial delivery system that ensured much better capability of inhibiting the growth of L. monocytogenes throughout 24 h incubation at 37 °C.

Brain natriuretic peptide (BNP) expressing sensory neurons are not involved in acute, inflammatory or neuropathic pain.

Background: We recently demonstrated that brain natriuretic peptide is expressed in the dorsal root ganglia, and that brain natriuretic peptide is required for normal detection of pruritogens. We further showed that the receptor for brain natriuretic peptide, natriuretic peptide receptor A, is present in the spinal cord, and elimination of these neurons profoundly attenuates scratching to itch-inducing compounds. However, the potential modulatory roles of brain natriuretic peptide in nociception, inflammation, and neuropathic mechanisms underlying the sensation of pain have not been investigated in detail. Findings: To demonstrate the involvement of brain natriuretic peptide in pain, we compared the behavioral responses of brain natriuretic peptide knockout mice with their wild-type littermates. First, we showed that brain natriuretic peptide is not required in chemically induced pain responses evoked by the administration of capsaicin, allyl isothiocyanate, adenosine 5'-triphosphate, or inflammatory soup. We further measured pain behaviors and found no involvement of brain natriuretic peptide in hot, cold, or mechanical nociceptive responses in mice, nor did we find evidence for the involvement of brain natriuretic peptide in neuroinflammatory sensitization elicited by complete Freund's adjuvant or in neuropathic pain. Conclusions: These results demonstrate that brain natriuretic peptide is not essential for pain-related behaviors.

Antibiotic sensitivity pattern of indigenous lactobacilli isolated from curd and human milk samples.

The gut microbiota plays a vital role in host well-being and lactic acid bacteria (LAB) have gained an overwhelming attention as health promoter. This perception has evolved from traditional dairy products to a money-spinning market of probiotics. The safety of probiotics is coupled to their intended use and LAB may act as pool of antimicrobial resistance genes that could be transferred to pathogens, either in food matrix or in gastrointestinal tract, which could be detrimental to host. This study evaluated the antibiotic susceptibility patterns of LAB isolated from curd (20) and human milk (11) samples. Antibiotic susceptibility was determined against 26 common antibiotics, following reference disc diffusion assay. A varied response in terms of susceptibility and resistance towards antibiotics was recorded. Among curd isolates, D7 (Lactobacillus plantarum) was the most resistant followed by D4, D8, D10 and D25. Among human milk isolates, HM-1 (L. casei) showed the highest resistance profile. All LAB isolates displayed high susceptibility pattern towards imipenem and meropenem. In general, high resistivity was exhibited by human milk isolates. The present study showed that antibiotic resistance is widespread among different lactobacilli, which may pose a food safety concern. Therefore, antibiotic sensitivity should be considered as a vital tool for safety assessment of probiotics.

Antibacterial effects of Lactobacillus isolates of curd and human milk origin against food-borne and human pathogens.

This study was undertaken to assess the antibacterial efficacy of lactobacilli isolated from curd and human milk samples. Identities of thirty-one different lactobacilli (20 from curd and 11 from human milk) were confirmed by genus-specific PCR and 16S rRNA-based sequencing. These strains belonged to five species, Lactobacillus casei, L. delbrueckii, L. fermentum, L. plantarum, and L. pentosus. Antibacterial activities of cell-free supernatants (CFSs) of all the Lactobacillus isolates were estimated through standard agar-well diffusion assay, against commonly occurring food-borne and clinically important human pathogens. None of the lactobacilli cell-free supernatant (CFS) exhibited inhibitory activity against four pathogens, namely Staphylococcus aureus, Listeria monocytogenes, Escherichia coli, and Klebsiella pneumoniae. Bacillus cereus, Salmonella enterica serovar Typhi, and Shigella flexneri were moderately inhibited by majority of CFSs, whereas, weak activity was observed against Pseudomonas aeruginosa and Proteus mirabilis. CFS of some of the curd isolates displayed antagonistic activity against Streptococcus mutans; however, human milk lactobacilli did not displayed any inhibitory activity against them. As expected, Nisin (Nisaplin®) showed inhibitory activity against Gram-positive, S. aureus, B. cereus, and L. monocytogenes. Interestingly, few of the examined CFSs exhibited inhibitory activities against both Gram-positive and Gram-negative pathogens. Findings from this study support the possibility to explore the tested lactobacilli and their CFSs as natural bio-preservatives, alone or in combination with approved bacteriocins in food and pharma formulations after validating their safety.

Subchronic Arsenic Exposure Through Drinking Water Alters Lipid Profile and Electrolyte Status in Rats.

Arsenic is a groundwater pollutant and can cause various cardiovascular disorders in the exposed population. The aim of the present study was to assess whether subchronic arsenic exposure through drinking water can induce vascular dysfunction associated with alteration in plasma electrolytes and lipid profile. Rats were exposed to arsenic as 25, 50, and 100 ppm of sodium arsenite through drinking water for 90 consecutive days. On the 91st day, rats were sacrificed and blood was collected. Lipid profile and the levels of electrolytes (sodium, potassium, and chloride) were assessed in plasma. Arsenic reduced high-density lipoprotein cholesterol (HDL-C) and HDL-C/LDL-C ratio, but increased the levels of triglycerides, total cholesterol, low-density lipoprotein cholesterol (LDL-C), and electrolytes. The results suggest that the arsenic-mediated dyslipidemia and electrolyte retention could be important mechanisms in the arsenic-induced vascular disorder.

BAY 41-2272 Treatment Improves Acetylcholine-Induced Aortic Relaxation in L-NAME Hypertensive Rats.

Hypertension, an emerging problem of recent era, and many pathophysiological factors are participating to produce the disease. Nitric oxide (NO) is an important constituent to ameliorate hypertensive condition. Inhibition of endogenous NO synthase by L-NG-Nitroarginine methyl ester (L-NAME) was responsible for generating hypertension in rats. BAY 41-2272 (5-cyclopropyl-2-[1-(2-fluoro-benzyl)-1H-pyrazolo[3,4-b]pyridine-3-yl]-pyrimidin-4-ylamine), a soluble guanylyl cyclase activator, restricts rise of blood pressure and shows cardioprotective activity. The aim of the present study was to analyze effect of short-term BAY 41-2272 treatment on blood pressure and vascular function. Male Wistar rats were randomly divided into three groups such as control (group-A), hypertensive (group-B), and BAY 41-2272-treated hypertensive (group-C) rats. Normal saline was administered intramuscularly to control rats for last 3 days (days 40, 41, and 42) of total 42 days treatment, whereas rats of group-B and group-C were treated with L-NAME hydrochloride in drinking water at 50 mg/kg body weight daily for 42 days. Also, normal saline and BAY 41-2272 were administered for last 3 days at two different dosages at 1 and 3 mg/kg body weight/day intramuscularly to group-B and group-C rats, respectively. Administration of BAY 41-2272 for 3 days was not sufficient enough to decrease mean arterial pressure of hypertensive rats significantly. BAY at both the treatment dosages significantly ameliorate acetylcholine-induced maximal aortic relaxation compared with BAY-untreated hypertensive rats. Findings of the present study indicate that even shorter period of BAY 41-2272 treatment (3 days) improves vascular relaxation.

NO synthase inhibition attenuates EDHF-mediated relaxation induced by TRPV4 channel agonist GSK1016790A in the rat pulmonary artery: Role of TxA2.

BACKGROUND: The aim of the present study was to observe the concomitant activation of nitric oxide (NO) and endothelium-derived hyperpolarizing factor (EDHF) pathways by TRPV4 channel agonist GSK1016790A in the rat pulmonary artery and explore the mechanism by which NO synthase inhibition attenuates EDHF-mediated relaxation in endothelium-intact rat pulmonary artery. METHODS: Tension experiments were conducted on the pulmonary artery from male Wistar rats. RESULTS: TRPV4 channel agonist GSK1016790A (GSK) caused concentration-dependent relaxation (Emax 86.9±4.6%; pD2 8.7±0.24) of the endothelium-intact rat pulmonary artery. Combined presence of apamin and TRAM-34 significantly attenuated the relaxation (Emax 61.1±6.0%) to GSK. l-NAME (100µM) significantly attenuated (8.2±2.9%) the relaxation response to GSK that was resistant to apamin plus TRAM-34. However, presence of ICI192605 or furegrelate alongwith l-NAME revealed the GSK-mediated EDHF-response (Emax of 28.5±5.2%; Emax 24.5±4.3%) in this vessel, respectively. Further, these two TxA2 modulators (ICI/furegrelate) alongwith l-NAME had no effect on SNP-induced endothelium-independent relaxation in comparison to l-NAME alone. This EDHF-mediated relaxation was sensitive to inhibition by K(+) channel blockers apamin and TRAM-34 or 60mMK(+) depolarizing solution. Further, combined presence of apamin and TRAM-34 in U46619 pre-contracted pulmonary arterial rings significantly reduced the maximal relaxation (Emax 71.6±6.9%) elicited by GSK, but had no effect on the pD2 (8.1±0.03) of the TRPV4 channel agonist in comparison to controls (Emax, 92.4±4.3% and pD2, 8.3±0.06). CONCLUSION: The present study suggests that NO and EDHF are released concomitantly and NO synthase inhibition attenuates GSK-induced EDHF response through thromboxane pathway in the rat pulmonary artery.

Erythropoietin Reverses Sepsis-Induced Vasoplegia to Norepinephrine Through Preservation of α1D-Adrenoceptor mRNA Expression and Inhibition of GRK2-Mediated Desensitization in Mouse Aorta.

We investigated the effect of erythropoietin (EPO) posttreatment on survival time and vascular functions in a mouse model of sepsis. Sepsis was induced by cecal ligation and puncture. After 20 ± 2 hours of sepsis, thoracic aorta was isolated for assessing its reactivity to norepinephrine (NE) and acetylcholine (ACh). We also measured the tissue nitric oxide (NO) level, inducible nitric oxide synthase (iNOS), endothelial nitric oxide synthase (eNOS), G protein-coupled receptor kinase 2 (GRK2), and α1D adrenoceptor messenger RNA (mRNA)/protein expression. In septic mice, EPO moderately improved the survival time from 19.68 ± 0.75 to 34.7 ± 3.2 hours. Sepsis significantly decreased the aortic contractile response to NE along with reduced α1D mRNA and protein expression. Erythropoietin significantly preserved the α1D receptor expression and restored NE-induced contractions to control levels in septic mice. Further, it attenuated the aortic α1D receptor desensitization in sepsis which was evident from reduced GRK2 mRNA expression. Accordingly, a selective GRK2 inhibitor markedly restored the contractile responses to NE in sepsis. Erythropoietin treatment attenuated iNOS mRNA expression and iNOS-induced overproduction of NO, but improved endothelium-dependent relaxation to ACh associated with increased eNOS mRNA expression. In conclusion, EPO seems to reverse sepsis-induced vasoplegia to NE through the preservation of α1D adrenoceptor mRNA/protein expression, inhibition of GRK2-mediated desensitization, and attenuation of NO overproduction in the mouse aorta.

Oral administration of veratric acid, a constituent of vegetables and fruits, prevents cardiovascular remodelling in hypertensive rats: a functional evaluation.

In our previous studies, veratric acid (VA) shows beneficial effect on hypertension and its associated dyslipidaemia. In continuation, this study was designed to investigate the effect of VA, one of the major benzoic acid derivatives from vegetables and fruits, on cardiovascular remodelling in hypertensive rats, primarily assessed by functional studies using Langendorff isolated heart system and organ bath system. Hypertension was induced in male albino Wistar rats by oral administration of N ω -nitro-l-arginine methyl ester hydrochloride (l-NAME) (40 mg/kg body weight (b.w.)) in drinking water for 4 weeks. VA was orally administered at a dose of 40 mg/kg b.w. l-NAME-treated rats showed impaired cardiac ventricular and vascular function, evaluated by Langendorff isolated heart system and organ bath studies, respectively; a significant increase in the lipid peroxidation products such as thiobarbituric acid-reactive substances and lipid hydroperoxides in aorta; and a significant decrease in the activities of superoxide dismutase, catalase, glutathione peroxidase and levels of GSH, vitamin C and vitamin E in aorta. Fibrotic remodelling of the aorta and heart were assessed by Masson's Trichrome staining and Van Gieson's staining, respectively. In addition, l-NAME rats showed increased heart fibronectin expression assessed by immunohistochemical analysis. VA supplementation throughout the experimental period significantly normalised cardiovascular function, oxidative stress, antioxidant status and fibrotic remodelling of tissues. These results of the present study conclude that VA acts as a protective agent against hypertension-associated cardiovascular remodelling.

Atorvastatin along with imipenem attenuates acute lung injury in sepsis through decrease in inflammatory mediators and bacterial load.

Lung is one of the vital organs which is affected during the sequential development of multi-organ dysfunction in sepsis. The purpose of the present study was to examine whether combined treatment with atorvastatin and imipenem could attenuate sepsis-induced lung injury in mice. Sepsis was induced by caecal ligation and puncture. Lung injury was assessed by the presence of lung edema, increased vascular permeability, increased inflammatory cell infiltration and cytokine levels in broncho-alveolar lavage fluid (BALF). Treatment with atorvastatin along with imipenem reduced the lung bacterial load and pro-inflammatory cytokines (IL-1ß and TNFα) level in BALF. The markers of pulmonary edema such as microvascular leakage and wet-dry weight ratio were also attenuated. This was further confirmed by the reduced activity of MPO and ICAM-1 mRNA expression, indicating the lesser infiltration and adhesion of inflammatory cells to the lungs. Again, expression of mRNA and protein level of iNOS in lungs was also reduced in the combined treatment group. Based on the above findings it can be concluded that, combined treatment with atorvastatin and imipenem dampened the inflammatory response and reduced the bacterial load, thus seems to have promising therapeutic potential in sepsis-induced lung injury in mice.