Endothelial-dependent relaxation of α-pinene and two metabolites, myrtenol and verbenol, in isolated murine blood vessels.

Epidemiological evidence shows that residential proximity to greenspaces is associated with lower risk of all-cause and cardiovascular mortality; however, the mechanism(s) underlying this link remains unclear. Plants emit biogenic volatile organic compounds such as α-pinene that could elicit beneficial cardiovascular effects. To explore the role of α-pinene more directly, we studied the metabolism and the vascular effects of α-pinene. We found that exposure of mice to α-pinene (1 ppm, 6 h) generated two phase I oxidation metabolites, cis- and trans-verbenol [(1R,2R,5R)-verbenol and (1 R,2S,5R)-verbenol)] and myrtenol [(1S,5R)-(+)-myrtenol] that were identified in urine by GC-MS. Precontracted naïve murine male and female aorta and superior mesenteric artery (SMA) were relaxed robustly (60% tension reduction) by increasing concentrations of α-pinene, myrtenol, and verbenol to 0.3 mM, whereas 1 mM α-pinene was vasotoxic. The SMA was six times more sensitive than the aorta to α-pinene. Both myrtenol and verbenol were equally potent and efficacious as parent α-pinene in male and female SMA. The sensitive portion of the α-pinene-, myrtenol-, and verbenol-induced relaxations in male SMA was mediated by 1) endothelium, 2) eNOS-derived NO, and 3) guanylyl cyclase (GC) activity. Moreover, α-pinene activated the transient receptor potential ankyrin-1 (TRPA1) channel whereas the metabolites did not. Endothelial-derived NO regulates blood flow, blood pressure, and thrombosis, and it is plausible that inhaled (and ingested) α-pinene (or its metabolites) augments NO release to mediate the cardiovascular benefits of exposure to greenness.NEW & NOTEWORTHY A common plant-derived biogenic volatile organic compound, α-pinene, and two of its metabolites, myrtenol and verbenol, stimulate vasorelaxation in murine superior mesenteric artery. Both α-pinene- and its metabolites induce vasorelaxation by activation of the endothelium, nitric oxide, and guanylyl cyclase. α-Pinene also activates the transient receptor potential ankyrin-1. Positive associations between greenness exposure and human cardiovascular health may be a result of the vascular action of α-pinene and its metabolites, a novel consideration.

Acrolein but not its metabolite, 3-Hydroxypropylmercapturic acid (3HPMA), activates vascular transient receptor potential Ankyrin-1 (TRPA1): Physiological to toxicological implications.

Acrolein, an electrophilic α,ß-unsaturated aldehyde, is present in foods and beverages, and is a product of incomplete combustion, and thus, reaches high ppm levels in tobacco smoke and structural fires. Exposure to acrolein is linked with cardiopulmonary toxicity and cardiovascular disease risk. The hypothesis of this study is the direct effects of acrolein in isolated murine blood vessels (aorta and superior mesenteric artery, SMA) are transient receptor potential ankyrin-1 (TRPA1) dependent. Using isometric myography, isolated aorta and SMA were exposed to increasing levels of acrolein. Acrolein inhibited phenylephrine (PE)-induced contractions (approximately 90%) in aorta and SMA of male and female mice in a concentration-dependent (0.01-100 µM) manner. The major metabolite of acrolein, 3-hydroxypropylmercapturic acid (3HPMA), also relaxed PE-precontracted SMA. As the SMA was 20× more sensitive to acrolein than aorta (SMA EC50 0.8 ± 0.2 µM; aorta EC50 > 29.4 ± 4.4 µM), the mechanisms of acrolein-induced relaxation were studied in SMA. The potency of acrolein-induced relaxation was inhibited significantly by: 1) mechanically-impaired endothelium; 2) Nω-Nitro-L-arginine methyl ester hydrochloride (L-NAME); 3) guanylyl cyclase (GC) inhibitor (ODQ); and, 4) a TRPA1 antagonist (A967079). TRPA1 positive immunofluorescence was present in the endothelium. Compared with other known TRPA1 agonists, including allyl isothiocyanate (AITC), cinnamaldehyde, crotonaldehyde, and formaldehyde, acrolein stimulated a more potent TRPA1-dependent relaxation. Acrolein, at high concentration [100 µM], induced tension oscillations (spasms) independent of TRPA1 in precontracted SMA but not in aorta. In conclusion, acrolein is vasorelaxant at low levels (physiological) yet vasotoxic at high levels (toxicological).

Design and rationale of the atrial fibrillation occurring transiently with stress (AFOTS) incidence study.

BACKGROUND: Atrial fibrillation (AF) is often detected for the first time in patients hospitalized for medical illness or non-cardiovascular surgery. AF occurring transiently with stress (AFOTS) describes this manifestation of AF, which may either be the result of a non-cardiac stressor, or existing paroxysmal AF that was not previously detected. Current estimates of AFOTS incidence are imprecise: ranging from 1 to 44%, owing to the marked heterogeneity in patient populations, identification and methods used to detect AFOTS. METHODS: The prospective, two-centre epidemiological AFOTS Incidence study will enroll 250 consecutive participants without a history of AF but with at increased risk of AF (Age ≥ 65 or >50 with one risk factor for AF) admitted to intensive care units (ICUs) for medical illness or non-cardiac surgery. Upon admission, participants will wear an ECG patch monitor that will remain in place for 14 days, or until discharge from hospital. Patients' consent to participation is deferred for up to 72 h after admission. The primary endpoint is the incidence of AF lasting ≥30 s. The study is powered to detect an AF incidence of 17% ±â€¯5%. RESULTS: We conducted a vanguard feasibility study, and 55 participants have completed participation. The median duration of monitoring was seven days. AF was detected by the clinical team in 8 participants (14%; 95% Confidence Interval 7-26%). CONCLUSIONS: The AFOTS Incidence study will employ a systematic and highly sensitive protocol for detecting AFOTS in medical illness and non-cardiac surgery ICU patients. This study is feasible and will provide a reliable estimate of the true incidence of AFOTS in this population.

Inscription of type I and depressed cladding waveguides in lithium niobate using a femtosecond laser.

We describe two types of waveguides (type I and depressed cladding) inscribed in lithium niobate using a variable repetition rate (200 kHz-25 MHz), 270 fs duration fiber laser. The type I modification-based waveguides have propagation losses in the range from 1.2 to 10 dB/cm at 1550 nm, depending on experimental parameters. These waveguides are not permanent; they deteriorate over time. Such deterioration of waveguides can be slowed down from 30 days to 100 days by pre-annealing the samples and by writing at a 720 kHz laser repetition rate. The propagation losses measured at 1550 nm show significant improvement for pre-annealed samples. The depressed cladding-inscribed waveguides are permanent, but the propagation loss depends on the number of damage tracks. A track separation of ∼1 µm between adjacent damage tracks yields the lowest propagation loss of 0.5 dB/cm at 1550 nm for a 40 µm diameter waveguide. We observe multimode guidance for sizes in the range of 20-80 µm in these waveguide structures at 1550 nm. Their crystalline nature is found to remain intact, as inferred from second-harmonic generation within the waveguide region.

Role of altered mitochondria functions in the pathogenesis of systemic lupus erythematosus.

Mitochondria, main producers of reactive-oxygen species (ROS), were studied to examine their role in the pathogenesis of systemic lupus erythematosus (SLE). PBMCs and mitochondria were isolated from SLE patients and healthy volunteers for various parameters. Mitochondrial ROS, swelling, hyperpolarization and levels of cytochrome c, caspase3 in the cells were assessed by flow cytometry. ROS was significantly increased in SLE patients (SLE vs controls: 1.83 ± 1.03 vs 1.10 ± 0.35; p < 0.0001). Depolarized state of mitochondria was greater in patients (SLE vs controls: 7.10 ± 5.50% vs 2.5 ± 1.8%; p < 0.05). Mitochondria swelling was found to be significantly altered in patients (SLE vs controls: 112.65 ± 36.56 vs 60.49 ± 20.69; p < 0.001). Expression of cytochrome c and caspase 3 (SLE vs controls: 1.37 ± 0.37% vs 1.01 ± 0.03%; 1.57 ± 0.46% vs 1.06 ± 0.07%; p < 0.05) respectively was found to be significantly increased in SLE. Further, the enzymatic activity of mitochondrial complex was assessed in isolated mitochondria. A significant decrease in activity of Complex I (SLE vs controls: 11.79 ± 3.18 vs 15.10 ± 6.38 nmol NADH oxidized/min/mg protein, p < 0.05); Complex IV (SLE vs control: 9.41 ± 5.16 vs 13.56 ± 5.92 nmol cytochrome c oxidized/min/mg protein, p < 0.05) and Complex V (SLE vs controls: 4.85 ± 1.39 vs 6.17 ± 2.02 nmol ATP hydrolyzed/min/mg protein, p < 0.05) was found in SLE patients in comparison to healthy controls. However, Complex II did not show significant variation in either group (SLE vs controls: 42.2 ± 28.6 vs 61.71 ± 42.3 nmol succinate oxidized/min/mg protein; ns). The decrease in enzyme activities of mitochondrial Complexes I, IV and V on one hand and ROS, hyperpolarization and apoptosis on the other points toward a possible role of mitochondria in the pathogenesis of lupus.

Curcumin-Mediated Reversal of p15 Gene Promoter Methylation: Implication in Anti-Neoplastic Action against Acute Lymphoid Leukaemia Cell Line.

Curcumin has been documented to exert anticancer effects by interacting with altered proliferative and apoptotic pathways in cancer models. In this study, we evaluated the potential of curcumin to reverse promoter methylation of the p15 gene in Raji cells and its ability to induce apoptosis and genomic instability. Anti-neoplastic action of curcumin showed an augmentation in reactive oxygen species (ROS) and cell cycle arrest in G1 phase. Subsequently, curcumin- exposed Raji cells showed structural abnormalities in chromosomes. These observations suggest that curcumin also causes ROS-mediated apoptosis and genomic instability. The treatment of Raji cell line with 10 µM curcumin caused hypomethylation of the p15 promoter after six days. Hypomethylation of p15 was further found to be favoured by downregulation of DNA methyltransferase 1 after 10 µM curcumin treatment for six days. Methylation-specific PCR suggested demethylation of the p15 promoter. Demethylation was further validated by DNA sequencing. Reverse-transcription PCR demonstrated that treatment with curcumin (10 µM) for six days led to the up-regulation of p15 and down-regulation of DNA methyltransferase 1. Furthermore, curcumin- mediated reversal of p15 promoter methylation might be potentiated by down-regulation of DNA methyltransferase 1 expression, which was supported by cell cycle analysis. Furthermore, curcumin acts as a double-pronged agent, as it caused apoptosis and promoter hypomethylation in Raji cells.

Quality characteristics and stability of Moringa oleifera seed oil of Indian origin.

Cold pressed and hexane extracted moringa seed oils (CPMSO and HEMSO) were evaluated for their physico-chemical and stability characteristics. The iodine value, saponification value and unsaponifiable matter of CPMSO and HEMSO were found to be 67.8 and 68.5 g I2 / 100 g oil, 190.4 and 191.2 mg KOH / g oil and 0.59 and 0.65%, respectively. The total tocopherols of CPMSO and HEMSO were found to be 95.5 and 90.2 mg/Kg. The fatty acid composition of CPMSO and HEMSO showed oleic acid as the major fatty acid (78-79%). The oxidative, thermal and frying stabilities of the CPMSO were compared with commercial raw and refined groundnut oil (GNO and RGNO). The CPMSO was of adequate thermal stability and better oxidative stability as it showed 79% lesser peroxide formation than GNO. The frying stability of CPMSO was better as it showed lower increase in free fatty acid (28%), peroxide value (10 meq O2/Kg) and color (25%) than RGNO (48%, 22 meq O2/kg and 52%, respectively) after frying.

Ras signaling pathway in the chemopreventive action of different ratios of fish oil and corn oil in experimentally induced colon carcinogenesis.

Dietary factors play a significant role in colon cancer. The essential polyunsaturated fatty acids (PUFAs), n-3 PUFAs, and n-6 PUFAs exert inverse effect on cancer. This study was designed to understand the mechanism of chemopreventive action of different ratios of fish oil (FO) and corn oil (CO) in colon carcinoma. Wistar rats were divided into 3 groups: Group 1 received purified diet whereas Groups 2 and 3 received modified diet with FO:CO (1:1) and FO:CO (2.5:1), respectively. The groups were further subdivided into controls receiving ethylenediamine-tetra acetic-acid and treated groups received dimethylhydrazine-dihydrochloride (DMH)/wk for 4 wk. Animals sacrificed 48 h after last injection constituted initiation phase and that sacrificed after 16 wk constituted post-initiation phase. Differential effect of different ratios of FO and CO was analyzed in isolated colonocytes. In both phases, DMH treatment showed an increase in pan Ras, Raf, MEK1/2, extracellular signal regulated kinase (Erk)1/2, and c-fos levels. Akt levels were increased in post-initiation phase only. Treatment with FO + CO (1:1) + DMH decreased pan Ras, MEK1/2 and Erk1/2 levels in post-initiation phase whereas Raf and c-fos were decreased in both phases. Treatment with FO + CO (2.5:1) + DMH decreased Ras, Raf, MEK1/2, Erk1/2, and c-fos levels in both phases. Akt was decreased in post-initiation phase only. The chemo-preventive action of FO and CO may be mediated by time- and dose-dependent effect.

Validated HPLC method for the simultaneous determination of taxol and ellagic acid in a Punica granatum fruit extract containing combination formulation.

A simple, rapid, precise and accurate isocratic reversed-phase high performance liquid chromatography (HPLC) method was developed and validated for the simultaneous determination of paclitaxel and ellagic acid in a combination nanoformulation. Separation was achieved using a 25 x 4.6 mm column, particle size 5 microm C18 reverse phase column (Luna), with a mobile phase consisting of methanol and 0.05% H3PO4, in gradient elution mode with a mobile phase flow rate of 1 mL/min, using UV visible detection at 230 nm. Sharp and well defined peaks were obtained at retention times of 13.75 min. and 11.6 min. for paclitaxel and ellagic acid, respectively. Regression analysis showed a good linear relationship (r2 = 0.996 +/- 0.0011) and (r2 = 0.993 +/- 0.0011) over wide ranges of 5-500 microg/ml and 1-500 microg/ml for paclitaxel and ellagic acid, respectively. LOD and LOQ of paclitaxel were 30 ng/ml and 100 ng/ml, respectively, while for ellagic acid LOD and LOQ were 300 ng/ml and 1 microg/ml, respectively. The accuracy of the method was determined by recovery studies using the standard addition method and was found to be in the range of 99.61-101.21% and 98.70-102.22% for paclitaxel and ellagic acid, respectively. The relative standard deviation (% RSD) for precision, repeatability and robustness was less than 2%. The ellagic acid content in fruits of Punica granatum and combination formulation with paclitaxel was analyzed and found to be 0.04% w/w and 0.0012%w/w, respectively. The proposed, developed and validated HPLC method for the simultaneous quantification of ellagic acid and paclitaxel can be used for the quality control and standardization of several crude drugs and different combination formulations, in which ellagic acid is present.

Rare case of Servelle Martorelle Syndrome.

Servelle Martorelle Syndrome is a congenital vascular malformation associated with soft tissue hypertrophy and bony hypoplasia. This rarely involves whole of an extremity, with involvement of part of limbs reported in literature. We present a case of a twelve year boy who presented to the Department of Plastic Surgery SGPGIMS in April 2011 ,with history of circumferential soft tissue hypertrophy involving whole of left upper limb, scapular region and axilla since birth. The entire left upper limb length was lesser than the right upper limb. Hence this is a very rare case of Servelle Martorelle Syndrome having extensive limb involvement at a very young age. Highlighted is the role of conservative treatment and close follow-up to understand the natural history of the diseases, with prompt treatment of complications.

Glomus tumour of the nipple in a male patient.

A glomus tumour is a benign mesenchymal tumour. It is extremely rare in the breast. We report a case of glomus tumour of the nipple in a 54-year-old man. To the best of the authors' knowledge, this is the first case report of a glomus tumour of the nipple. We describe the different presenting symptoms, method of diagnosis and treatment.

Surveillance of RNase P, PMMoV, and CrAssphage in wastewater as indicators of human fecal concentration across urban sewer neighborhoods, Kentucky.

Wastewater surveillance has been widely used as a supplemental method to track the community infection levels of severe acute respiratory syndrome coronavirus 2. A gap exists in standardized reporting for fecal indicator concentrations, which can be used to calibrate the primary outcome concentrations from wastewater monitoring for use in epidemiological models. To address this, measurements of fecal indicator concentration among wastewater samples collected from sewers and treatment centers in four counties of Kentucky (N = 650) were examined. Results from the untransformed wastewater data over 4 months of sampling indicated that the fecal indicator concentration of human ribonuclease P (RNase P) ranged from 5.1 × 101 to 1.15 × 106 copies/ml, pepper mild mottle virus (PMMoV) ranged from 7.23 × 103 to 3.53 × 107 copies/ml, and cross-assembly phage (CrAssphage) ranged from 9.69 × 103 to 1.85 × 108 copies/ml. The results showed both regional and temporal variability. If fecal indicators are used as normalization factors, knowing the daily sewer system flow of the sample location may matter more than rainfall. RNase P, while it may be suitable as an internal amplification and sample adequacy control, has less utility than PMMoV and CrAssphage as a fecal indicator in wastewater samples when working at different sizes of catchment area. The choice of fecal indicator will impact the results of surveillance studies using this indicator to represent fecal load. Our results contribute broadly to an applicable standard normalization factor and assist in interpreting wastewater data in epidemiological modeling and monitoring.

Role of reactive intermediates in the immunopathogenesis of the pristane-induced Balb/c model of lupus.

Pristane-induced lupus in Balb/c mice represents an environmentally induced lupus model which is widely used for unravelling the mystery of the pathogenesis of the disease. An intraperitoneal innate immune reaction to pristane is primarily accountable for the development of the systemic lupus erythematosus-like disease in the model. In this study, reactive oxygen species (ROS) and nitric oxide (NO) levels were assessed (as a measure of chronic inflammation) in the peritoneum of the Balb/c model of SLE-like disease 6 months after a single intraperitoneal injection of pristane. Levels of ROS in peritoneal macrophages were significantly enhanced (mean fluorescence value ± SD: 648 ± 100.9) in pristane-treated mice (PT) as compared with control mice (mean fluorescence value ± SD: 79 ± 7.8) treated with phosphate buffer saline (PBST). An immunofluorescence study reveal the localization of ROS within nuclei, suggesting oxidative damage. Similarly, levels of NO were also markedly raised in PT mice (34.71 µmol/l ± 8.48) as compared with PBST mice (1.36 nmol/l ± 0.14). These new findings lead to speculation about the role of reactive intermediates in the development of disease. This study proposes that the sustained production of reactive intermediates during chronic intraperitoneal inflammation might reduce antioxidant defences and lead to a condition of oxidative stress, which might further be responsible for this autoimmune condition.

sof gene as a specific genetic marker for detection of Streptococcus pyogenes causing pharyngitis and rheumatic heart disease.

Streptococcus pyogenes is a human pathogen causing invasive and non—invasive diseases, as well as severe sequels, such as rheumatic fever. Rheumatic heart disease is a sequel of rheumatic fever results from an untreated strep throat causing damage of the heart valves. The usual detection methods of strep throat are culture, virulent test, antibiotic sensitivity, CRP, ESR and PCR. These methods are expensive, time consuming and have some limitations. All reported PCR methods are based on either 16S rRNA or specific gene based along with other methods to confirm the disease in more than 1h. Here, we have developed a PCR based diagnosis of streptococcus pyogenes using specific primers of virulent sof gene (serum opacity factor) of S. pyogenes. Our method is an improvement of the existing methods and the overall analysis completes in 1 h which is the least time reported so far for the confirmation of the disease. Amplicon of 228 bp of sof gene does not show homology with other organisms and can be used as genetic marker for S. pyogenes.

A comparative evaluation of iliac crest bone graft with and without injectable and advanced platelet rich fibrin in secondary alveolar bone grafting for cleft alveolus in unilateral cleft lip and palate patients: A randomized prospective study.

PURPOSE: Platelet rich fibrin enhances bone healing and results in better graft intake and helps in faster periodontal healing. In this study we have used a combination of two newly developed forms of platelet rich fibrin: injectable and advanced along with iliac bone graft for secondary alveolar bone grafting and compared it with cases in which only iliac bone graft was used. METHODS: 30 patients with alveolar cleft, with age group of ≥7 years, having complete unilateral cleft alveolus were included and divided into 2 groups of 15 patients each randomly. In Group A, secondary alveolar bone grafting was done using iliac bone graft along with injectable and advanced palate rich fibrin and in Group B, secondary alveolar bone grafting was done only with iliac bone graft. Success of the treatment was assessed using radiographic and clinical methods which included: The bone resorption of the interalveolar septum height of the teeth adjacent to the cleft, evaluated as per Bergland classification, assessment of periodontal status of the teeth adjacent to cleft alveolus. RESULTS: After 3 months and 6 months postoperatively: study group had better overall scores as per Bergland criteria. Periodontal status improved in both groups but was more in study group compared to control group. For both evaluations the data was clinically favorable in the study group. CONCLUSION: On preliminary investigations it shows that combination of injectable and advanced platelet rich fibrin seems to enhance bone formation in alveolar clefts when admixed with autologous cancellous bone harvested from the iliac crest than using iliac bone graft alone. It also reduces the chances of bone resorption and show higher percentage of bone volume. Secondary alveolar grafting improves periodontal health around the cleft alveolus.

Wastewater Sample Site Selection to Estimate Geographically Resolved Community Prevalence of COVID-19: A Sampling Protocol Perspective.

Wastewater monitoring for virus infections within communities can complement conventional clinical surveillance. Currently, most SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) clinical testing is voluntary and inconsistently available, except for a few occupational and educational settings, and therefore likely underrepresents actual population prevalence. Randomized testing on a regular basis to estimate accurate population-level infection rates is prohibitively costly and is hampered by a range of limitations and barriers associated with participation in clinical research. In comparison, community-level fecal monitoring can be performed through wastewater surveillance to effectively surveil communities. However, epidemiologically defined protocols for wastewater sample site selection are lacking. Herein, we describe methods for developing a geographically resolved population-level wastewater sampling approach in Jefferson County, Kentucky, and present preliminary results. Utilizing this site selection protocol, samples (n = 237) were collected from 17 wastewater catchment areas, September 8 to October 30, 2020 from one to four times per week in each area and compared to concurrent clinical data aggregated to wastewater catchment areas and county level. SARS-CoV-2 RNA was consistently present in wastewater during the studied period, and varied by area. Data obtained using the site selection protocol showed variation in geographically resolved wastewater SARS-CoV-2 RNA concentration compared to clinical rates. These findings highlight the importance of neighborhood-equivalent spatial scales and provide a promising approach for viral epidemic surveillance, thus better guiding spatially targeted public health mitigation strategies.

Worldwide prevalence, genotype distribution and management of hepatitis C.

Hepatitis C virus (HCV) is one of the leading causes of chronic liver disease, cirrhosis, and hepatocellular carcinoma, resulting in major global public health concerns. The HCV infection is unevenly distributed worldwide, with variations in prevalence across and within countries. The studies on molecular epidemiology conducted in several countries provide an essential supplement for a comprehensive knowledge of HCV epidemiology, genotypes, and subtypes, along with providing information on the impact of current and earlier migratory flows. HCV is phylogenetically classified into 8 major genotypes and 57 subtypes. HCV genotype and subtype distribution differ according to geographic origin and transmission risk category. Unless people with HCV infection are detected and treated appropriately, the number of deaths due to the disease will continue to increase. In 2015, 1.75 million new viral infections were mostly due to unsafe healthcare procedures and drug use injections. In the same year, access to direct-acting antivirals was challenging and varied in developing and developed countries, affecting HCV cure rates based on their availability. The World Health Assembly, in 2016, approved a global strategy to achieve the elimination of the HCV public health threat by 2030 (by reducing new infections by 90% and deaths by 65%). Globally, countries are implementing policies and measures to eliminate HCV risk based on their distribution of genotypes and prevalence.

A rapid assessment of wastewater for genomic surveillance of SARS-CoV-2 variants at sewershed scale in Louisville, KY.

In this communication, we report on the genomic surveillance of SARS-CoV-2 using wastewater samples in Jefferson County, KY. In February 2021, we analyzed seven wastewater samples for SARS-CoV-2 genomic surveillance. Variants observed in smaller catchment areas, such as neighborhood manhole locations, were not necessarily consistent when compared to associated variant results in downstream treatment plants, suggesting catchment size or population could impact the ability to detect diversity.

Cardioprotection and the mitochondrial permeability transition.

Although in developed countries, the rates of cardiovascular mortality show a decreasing trend, both the incidence and the prevalence of cardiovascular disease are on the rise in developing countries. It is likely that the currently unfolding epidemics of diabetes and obesity will erode recent gains in decreasing cardiovascular mortality in the Western countries as well. This article will focus on recent research which suggests that induction of mitochondrial permeability transition (MPT) during ischemia/ reperfusion (I/R) injury is a critical event that triggers both necrotic and apoptotic cell death. Additionally we will examine mechanisms that limit or prevent MPT which may be targeted to decrease ischemic cell death and to promote postischemic recovery of the heart. Nevertheless, the role of the mitochondria in myocardial I/R injury is complex and the signal transduction mechanisms that regulate MPT and its downstream consequences remain unclear and represent the current focus of several strategies of cardioprotection. Decades of exploration of the mitochondrial domains and the role of these organelles in regulating cell death and ischemic injury have brought us to a place where clinical interventions to limit infarct size seem to be realizable possibilities. The purpose of this review is to examine the possibility that inhibition of MPT may provide a clinically relevant target for decreasing I/R injury. Understanding MPT provide new insight into the role mitochondria play in decisions of cell survival and death.