High-fat diet-induced mitochondrial dysfunction is associated with loss of protection from ischemic preconditioning in renal ischemia reperfusion.

Consumption of high-fat diet (HFD) promotes mitochondrial dysfunction and the latter act as a critical factor in determining the severity of ischemia-reperfusion (IR) injury in different cell types. Ischemic preconditioning (IPC), a well-known protocol that render IR protection in kidney works via mitochondria. In the present study, we evaluated how HFD kidney with underlying mitochondrial changes respond to precondition protocol after IR induction. Wistar male rats were used in this study and were divided into two groups: SD (standard diet; n = 18) and HFD (high-fat diet; n = 18), which were further subdivided into sham, ischemia-reperfusion, and precondition groups at the end of the dietary regimen. Blood biochemistry, renal injury marker, creatinine clearance (CrCl), mitochondrial quality (fission, fusion, and phagy), mitochondrial function via ETC enzyme activities and respiration, and signalling pathway were analysed. Sixteen weeks of HFD administration to the rat deteriorated the renal mitochondrial health measured via 10% decline in mitochondrial respiration index ADP/O (in GM), reduced mitochondrial copy number (55%), biogenesis (56%), low bioenergetics potential (19% complex I + III and 15% complex II + III), increased oxidative stress, and reduced expression of mitochondrial fusion genes compared with SD rats. IR procedure in HFD rat kidney inflicted significant mitochondrial dysfunction and further deteriorated copy number along with impaired mitophagy and mitochondrial dynamics. IPC could effectively ameliorate the renal ischemia injury in normal rat but failed to provide similar kind of protection in HFD rat kidney. Even though the IR-associated mitochondrial dysfunction in both normal and HFD rats were similar, the magnitude of overall dysfunction and corresponding renal injury and compromised physiology was high in HFD rats. This observation was further confirmed via in vitro protein translation assay in isolated mitochondria from normal and HFD rat kidney that showed significantly reduction in the response ability of mitochondria in HFD. In conclusion, the deteriorated mitochondrial function and its quality along with low mitochondrial copy number and downregulation of mitochondrial dynamic gene exhibited by HFD rat kidney augments the sensitivity of renal tissue towards the IR injury which leads to the compromised protective ability by ischemic preconditioning.

Impaired renal ischemia reperfusion recovery after bilateral renal artery ligation in rats treated with adenine: role of renal mitochondria.

Vascular calcification (VC) and ischemia reperfusion (IR) injury is characterised to have mitochondrial dysfunction. However, the impact of dysfunctional mitochondria associated with vascular calcified rat kidney challenged to IR is not explored and is addressed in the present study. Male Wistar rats were treated with adenine for 20 days to induce chronic kidney dysfunction and VC. After 63 days, renal IR protocol was performed with subsequent recovery for 24 h and 7 days. Various mitochondrial parameters and biochemical assays were performed to assess kidney function, IR injury and its recovery. Adenine-induced rats with VC, decreased creatinine clearance (CrCl), and severe tissue injury demonstrated an increase in renal tissue damage and decreased CrCl after 24 h of IR (CrCl in ml: IR-0.220.02, VC-IR-0.050.01). Incidentally, the 24 h IR pathology in kidney was similar in both VC-IR and normal rat IR. But, the magnitude of dysfunction was higher with VC-IR due to pre-existing basal tissue alterations. We found severed deterioration in mitochondrial quantity and quality supported by low bioenergetic function in both VC basal tissue and IR challenged sample. However, post 7 days of IR, unlike normal rat IR, VC rat IR did not improve CrCl and corresponding mitochondrial damage in terms of quantity and its function were observed. Based on the above findings, we conclude that IR in VC rat adversely affect the post-surgical recovery, mainly due to the ineffective renal mitochondrial functional restoration from the surgery.

The worm Adult Activity Test (wAAT): A de novo mathematical model for detecting acute chemical effects in Caenorhabditis elegans.

We have adapted a semiautomated method for tracking Caenorhabditis elegans spontaneous locomotor activity into a quantifiable assay by developing a sophisticated method for analyzing the time course of measured activity. The 16-h worm Adult Activity Test (wAAT) can be used to measure C. elegans activity levels for efficient screening for pharmacological and toxicity-induced effects. As with any apical endpoint assay, the wAAT is mode of action agnostic, allowing for detection of effects from a broad spectrum of response pathways. With caffeine as a model mild stimulant, the wAAT showed transient hyperactivity followed by reversion to baseline. Mercury chloride (HgCl2 ) produced an early dose-response hyperactivity phase followed by pronounced hypoactivity, a behavior pattern we have termed a toxicant "escape response." Methylmercury chloride (meHgCl) produced a similar pattern to HgCl2 , but at much lower concentrations, a weaker hyperactivity response, and more pronounced hypoactivity. Sodium arsenite (NaAsO2 ) and dimethylarsinic acid (DMA) induced hypoactivity at high concentrations. Acute toxicity, as measured by hypoactivity in C. elegans adults, was ranked: meHgCl > HgCl2 > NaAsO2 = DMA. Caffeine was not toxic with the wAAT at tested concentrations. Methods for conducting the wAAT are described, along with instructions for preparing C. elegans Habitation Medium, a liquid nutrient medium that allows for developmental timing equivalent to that found with C. elegans grown on agar with OP50 Escherichia coli feeder cultures. A de novo mathematical parametric model for adult C. elegans activity and the application of this model in ranking exposure toxicity are presented.

Hydrogen sulfide postconditioning rendered cardioprotection against myocardial ischemia-reperfusion injury is compromised in rats with diabetic cardiomyopathy.

The present study aimed to investigate the efficacy of hydrogen sulfide (H2S) post-conditioning (HPOC) against ischemia-reperfusion (I/R) challenged diabetic rat hearts with or without cardiomyopathy using the Langendorff perfusion system. Male Wistar rats were randomly divided into different groups such as normal, diabetes mellitus (DM), and diabetic cardiomyopathy (DCM). Hearts from these groups were subjected to normal perfusion, I/R, and HPOC and were analyzed for cardiac physiology, cardiomyocyte injury, mitochondrial function, oxidative stress, and H2S metabolism. The results showed that HPOC protocol reduced the cardiac injury and improved the haemodynamics in normal and DM effectively, but not in DCM (RPP in mmHg*beats/min*103: HPOC- 32 ± 2, DM-HPOC-19 ± 1, DCM-HPOC-6 ± 2, LVDP in mmHg: HPOC- 96 ± 3, DM-HPOC-73 ± 2, DCM-HPOC-50 ± 3). DCM rats at the basal level exhibited perturbed myocardial architecture, mitochondrial dysfunction, and impaired glycolytic flux that failed to improve by HPOC treatment after I/R. HPOC exhibited a nominal improvement in the gene expression and activities of the H2S metabolizing enzymes such as cystathionine beta-synthase, rhodanese, and cystathionine-gamma-lyase in DCM hearts. Collectively, our results suggest that altered myocardial architecture along with exacerbated oxidative stress and mitochondrial dysfunction contribute towards the failure of HPOC cardioprotection against I/R-induced myocardial tissue injury in DCM.

Exploration of mercaptoacetamide-linked pyrimidine-1,3,4-oxadiazole derivatives as DNA intercalative topo II inhibitors: Cytotoxicity and apoptosis induction.

The design and synthesis of a new series of mercaptoacetamide-linked pyrimidine-1,3,4-oxadiazole hybrids was accomplished. The in vitro cytotoxic potential of these new compounds was evaluated against lung cancer (A549), prostate cancer (PC-3, DU-145) and human embryonic kidney (HEK) cell lines. Compound 9p showed the highest potency on A549 cells with an IC50 value of 3.8 ± 0.02 µM. Moreover, 9p was found to be 25-fold more selective towards cancer cell lines than the non-cancerous (HEK) cell line. The target-based assay revealed the inhibition of the topoisomerase II enzyme by compound 9p. UV-visible spectroscopy, fluorescence, circular dichroism (CD), and viscosity studies inferred the intercalative property and effective binding of compound 9p with CT-DNA. Apoptosis induced by the compound 9p was observed by various morphological staining assays, i.e, DAPI, EtBr/AO. Further, the molecular modeling studies revealed the binding of compound 9p at the active site of the DNA-topoisomerase II complex while the physicochemical properties were in the recommended range. Finally, mercaptoacetamide-linked pyrimidine-1,3,4-oxadiazole derivatives can be considered as a promising scaffold for development as effective anticancer agents and topoisomerase II inhibitors.

Impact of air pollution on stunting among children in Africa.

BACKGROUND: Undernutrition is a global public health crisis, causing nearly half of deaths for children under age 5 years. Little is known regarding the impact of air pollution in-utero and early childhood on health outcomes related to undernutrition. The aim of our study is to evaluate the association of prenatal and early-life exposure to PM2.5 and child malnutrition as captured by the height-for-age z-score (HAZ), and stunting in 32 countries in Africa. We also evaluated critical windows of susceptibility during pregnancy to each environmental risk. METHODS: We linked nationally representative anthropometric data from 58 Demographic and Health Surveys (DHS) (n = 264,207 children < 5 years of age) with the average in-utero PM2.5 concentrations derived from satellite imagery. We then estimated associations between PM2.5 and stunting and HAZ after controlling for child, mother and household factors, and trends in time and seasonality. RESULTS: We observed lower HAZ and increased stunting with higher in-utero PM2.5 exposure, with statistically significant associations observed for stunting (OR: 1.016 (95% CI: 1.002, 1.030), for a 10 µg/m3 increase). The associations observed were robust to various model specifications. Wald tests revealed that sex, wealth quintile and urban/rural were not significant effect modifiers of these associations. When evaluating associations between trimester-specific PM2.5 levels, we observed that associations between PM2.5 and stunting was the largest. CONCLUSIONS: This is one of the first studies for the African continent to investigate in-utero and early-life exposure to PM2.5 is an important marker of childhood undernutrition. Our results highlight that PM2.5 concentrations need to be urgently mitigated to help address undernutrition in children on the continent.

Resveratrol-mediated cardioprotection against myocardial ischemia-reperfusion injury was revoked by statin-induced mitochondrial alterations.

Resveratrol is well known for its antioxidant potential and ability to preserve mitochondrial function, reported attenuating ischemia-reperfusion (IR) injury in the heart. The present study investigates resveratrol on IR injury in rat hearts treated with statin for 14 days. Male Wistar rats were used in this study, and statin-induced cardiac metabolic alterations were monitored after the administration of simvastatin (80 mg/kg). IR was instigated by the Langendroff perfusion system and measured the physiological and biochemical changes. The basal level changes in ECG, ANP, and BNP expression and CoenzymeQ10 level were altered in statin-treated animals compared to the normal rat heart. The animals treated with statin demonstrated higher IR injury (measured via low rate pressure product (88.4%), increased histological alterations, prominent mitochondrial dysfunction (NQR: IR-72%, Stat IR-67%; SQR: IR-71%, Stat IR-74%; COX: IR-58%, Stat IR-52%) than the normal rat heart underwent similar protocols. Administration of heart with resveratrol recovered the IR associated hemodynamic indices in normal heart subjected to IR but failed to impart a similar effect in the statin-treated heart. Our results demonstrated that resveratrol failed to reverse the IR-associated cardiac injury and functional abnormalities in statin-treated rat hearts subjected to IR but effective in IR challenged normal heart.

Performance on the mouse vibration actuating search task is compromised by sleep deprivation.

As we go about our daily routines we are continuously bombarded with environmental feedback that requires appraisal and response. Sleep loss can compromise the efficiency by which these cognitive processes function. Operationally, poor performance caused by insufficient sleep translates to increased health and safety risks in settings where attention and timely and/or accurate decisions to respond are critical (e.g., at work, on the road, etc.). Current rodent tasks that assess altered cognition after sleep deprivation (SD) do not accurately model the continuous multisensory feedback that informs goal-oriented behavior in humans. Herein, we describe the vibration actuating search task (VAST), which consists of a vibrating open field with pseudo-randomly selected entrance and target destination points. To successfully complete a trial, mice use feedback from rotary motor-induced floor vibrations to navigate from the entrance point to the target destination. Sets of 20 trials were conducted on 3 consecutive days, and before testing on the third day control mice were undisturbed while other mice were sleep deprived for 10 h. On the first 2 days mice learned the task with high success rates. Alternatively, VAST performance was compromised following SD as measured by increased failures in task completion, time to target, time spent immobile, and decreased speed as compared with undisturbed mice. The VAST enables the analysis of continuous feedback via multiple sensory modalities in mice and is applicable to a variety of operational settings.NEW & NOTEWORTHY The vibration actuating search task (VAST) is a novel performance assay that uses continuous auditory and haptic feedback to motivate and direct search behaviors in mice. The VAST is rapidly acquired by mice and performance is disrupted by sleep deprivation. The VAST has practical application in occupational settings. The cognitive aspects of the sensorimotor integration in the VAST may prove useful for rodent models of neurodegenerative disease.

Novel diindoloazepinone derivatives as DNA minor groove binding agents with selective topoisomerase I inhibition: Design, synthesis, biological evaluation and docking studies.

We present here-in the molecular design and chemical synthesis of a novel series of diindoloazepinone derivatives as DNA minor groove binding agents with selective topoisomerase I inhibition. The in vitro cytotoxicity of the synthesized compounds was evaluated against four human cancer cell lines including DU143, HEPG2, RKO and A549 in addition to non-cancerous immortalized human embryonic kidney cells (HEK-293). Compound 11 showed significant cytotoxicity against all the four human cancer cell lines with IC50 values ranging from 4.2 to 6.59 µM. 11 was also found to display 13-fold selective cytotoxicity towards A549 cancerous cells compared to the non-cancerous cell lines (HEK-293). The decatenation, DNA relaxation and intercalation assays revealed that the investigational compounds 10 and 11 act as highly selective inhibitors of Topo-I with DNA minor groove binding ability which was also supported by the results obtained from circular dichroism (CD), UV-visible spectroscopy and viscosity studies. Apoptosis induced by the lead 11 was observed using morphological observations, AO/EB and DAPI staining procedures. Further, dose-dependent increase in the depolarization of mitochondrial membrane was also observed through JC-1 staining. Annexin V-FITC/PI assay confirmed that 11 induced early apoptosis. Additionally, cell cycle analysis indicated that the cells were arrested at sub-G1 phase. Gratifyingly, in silico studies demonstrated promising interactions of 11 with the DNA and Topo I, thus supporting their potential DNA minor groove binding property with relatively selective Topo I inhibition compared to Topo II.

M-SAKHI-Mobile health solutions to help community providers promote maternal and infant nutrition and health using a community-based cluster randomized controlled trial in rural India: A study protocol.

Reduction of childhood stunting is difficult to achieve by interventions that focus only on improving nutrition during infancy. Comprehensive interventions that extend through the continuum of care from pregnancy to infancy are needed. Mobile phones are now successfully being used for behaviour change communication to improve health. We present the methodology of an mHealth intervention "Mobile Solutions Aiding Knowledge for Health Improvement" (M-SAKHI) to be delivered by rural community health workers or Accredited Social Health Activists (ASHAs) for rural women, below or up to 20 weeks of pregnancy through delivery until their infant is 12 months of age. This protocol paper describes the cluster randomized controlled trial to evaluate the effectiveness of M-SAKHI. The primary objective of the trial is to reduce the prevalence of stunting (height-for-age < -2 z-score) in children at 18 months of age by 8% in the intervention as compared with control. The secondary objectives include evaluating the impact on maternal dietary diversity, birth weight, infant and young child feeding practices, infant development, and child morbidity, along with a range of intermediate outcomes for maternal, neonatal, and infant health. A total of 297 ASHAs, five trained counsellors, and 2,501 participants from 244 villages are participating in this study. The outcome data are being collected by 51 field research officers. This study will provide evidence regarding the efficacy of M-SAKHI to reduce stunting in young children in rural India, and if effective, the cost-effectiveness of M-SAKHI.

Comparative Evaluation of N-Butyl Cyanoacrylate and Silk Sutures on Healing of Periodontal Flaps: A Clinico Histological Evaluation.

Background The periodontal flap is one of the most frequently employed procedures. Closure of reflected flap is important step in flap surgery. Black silk sutures are most often used material in routine surgical procedures. These suture materials demand more time and effort and expertise from the surgeon. Tissue adhesives have been developed as alternatives to overcome these problems such as cyanoacrylates. Objective The present study is an attempt to compare effectiveness of the black silk suture with cyanoacrylate adhesives in closing reflected periodontal flap. Method Thirty systemically healthy patients who underwent bilateral flap surgery were given 3-0 black silk sutures on one side and N-butyl cyanoacrylate adhesive on the other side to close a surgical incision. All the participants in the study were recalled on the seventh, 21st, 42nd day. Participants were evaluated for healing and plaque accumulation by assessing the gingival index, plaque index, wound healing index. Biopsy specimens were obtained on seventh and 42nd postoperative day. Result The amount of inflammation was less during the first week of healing when cyanoacrylate was compared with silk. However, over a period of 21 days to 42 days, the sites treated with both the materials showed similar healing patterns without any significant difference in the evaluated parameter. Conclusion The result of the study showed that the use of cyanoacrylate for the closure of periodontal flaps results in better initial post-operative healing as compared to closure with silk suture and that this method of closure can be advocated in a routine surgical periodontal practice.

Efficacy of Subgingivally Delivered Satranidazole in the Treatment of Type 2 Diabetes Subjects with Chronic Periodontitis: A Randomized Controlled Clinical Trial.

BACKGROUND: The present clinical trial was designed to investigate the effectiveness of subgingivally delivered satranidazole (SZ) gel as an adjunct to scaling and root planing (SRP) in the treatment of chronic periodontitis. METHODS: Sixty-four subjects with probing depth (PD) ≥ 5 mm and who were diagnosed with type 2 diabetes were selected. Thirty-two subjects each were randomly assigned to SRP + placebo (Group 1) and SRP + SZ (Group 2). The clinical outcomes evaluated were plaque index (PI), gingival index (GI), clinical attachment level (CAL) and PD at baseline, 1 month, 3-months and 6 months. RESULTS: At 6 months, Group 2 had greater mean reduction (4.73 mm) in PD as compared to Group 1 (2.09 mm; p < 0.05) and also a greater mean CAL gain (3.92 mm versus 1.64 mm; p < 0.05). CONCLUSION: The use of 3% SZ gel, when used as an adjunct to non-surgical periodontal therapy in subjects with periodontitis, achieves significantly better clinical results than initial periodontal treatment alone.

Clinical and microbiological effects of levofloxacin in the treatment of Aggregatibacter actinomycetemcomitans-associated periodontitis: a randomized placebo-controlled clinical trial.

AIM: To evaluate the clinical and microbiological effects of systemic levofloxacin (LFX) in subjects with Aggregatibacter actinomycetemcomitans-associated chronic periodontitis (AA-ACP). MATERIALS AND METHODS: Subjects with severe periodontitis with subgingival detection of A. actinomycetemcomitans were randomly divided into two treatment groups; a test group (n = 35) that received scaling and root planing (SRP) and LFX (500 mg o.d.) and a control group (n = 34) that received SRP and placebo (o.d.) for 10 days. Plaque index (PI), gingival index (GI), percent of sites with bleeding on probing (% BoP), probing depth (PD) and clinical attachment level (CAL) were recorded and subgingival plaque samples were cultivated for detection of A. actinomycetemcomitans at baseline to 6 months at various intervals. RESULTS: Subjects receiving LFX showed the greatest improvements in mean PD and CAL. The difference in the reduction of PD and CAL in the two groups was significant at 1, 3 and 6 months for PD and 3 and 6 months for CAL (p < 0.05). The inter-group difference in PI, GI and % BoP was not significant at any interval. Detectable levels of A. actinomycetemcomitans were significantly less in the test group 3 and 6 months post-therapy. CONCLUSION: Systemic LFX as an adjunct to SRP improves clinical outcomes and suppresses A. actinomycetemcomitans below detectable levels.

Does cardiac impairment develop in ischemic renal surgery in rats depending on the reperfusion time?

Background: Renal dysfunction is known to cause heart failure. However, renal dysfunction associated with kidney surgeries (mediated by reperfusion injury) that affects the cardiac physiological function, especially during the recovery and repair phase of renal surgery is unknown. Method: Male Wistar rats (238 ± 18 g) were subjected to renal sham and ischemia-reperfusion (IR-bilateral clamping for 15 min/45 min and reperfusion for 24 h/48 h/7 days) surgeries. At the end of the experiment, the heart was isolated from the animal (to exclude neurohormonal influence) and perfused for 60 min with Krebs-Hanseleit buffer to study the physiological changes. Result: Renal artery bilateral occlusion for 45 min that creates ischemia, followed by 24 h of reperfusion did not impart any significant cardiac physiological functional decline but 48 h of reperfusion exhibited a significant decline in cardiac hemodynamic indices (Rate pressure product in x104 mmHg*beats/min: Sham- 3.53 ± 0.19, I45_R48-2.82 ± 0.21) with mild tissue injury. However, 7 days of reperfusion inflict significant physiological decline (Rate pressure product in x104 mmHg*beats/min - 2.5 ± 0.14) and tissue injury (Injury score- 4 ± 1.5) in isolated rat hearts. Interestingly, when the renal artery bilateral occlusion time was reduced to 15 min the changes in the hearts were negligible after 7 days. Cellular level exploration reveals a positive relation between functional deterioration of mitochondria and elevated mitochondrial oxidative stress and inflammation with cardiac physiological decline and injury linked with renal ischemia-reperfusion surgery. Conclusion: Cardiac functional decline associated with renal surgery is manifested during renal repair or recovery. This decline depends on cardiac mitochondrial health, which is negatively influenced by the renal IR mediators and kidney function.

Evaluating the sensitivity of mortality attributable to pollution to modeling Choices: A case study for Colorado.

We evaluated the sensitivity of estimated PM2.5 and NO2 health impacts to varying key input parameters and assumptions including: 1) the spatial scale at which impacts are estimated, 2) using either a single concentration-response function (CRF) or using racial/ethnic group specific CRFs from the same epidemiologic study, 3) assigning exposure to residents based on home, instead of home and work locations for the state of Colorado. We found that the spatial scale of the analysis influences the magnitude of NO2, but not PM2.5, attributable deaths. Using county-level predictions instead of 1 km2 predictions of NO2 resulted in a lower estimate of mortality attributable to NO2 by âˆ¼ 50 % for all of Colorado for each year between 2000 and 2020. Using an all-population CRF instead of racial/ethnic group specific CRFs results in a 130 % higher estimate of annual mortality attributable for the white population and a 40 % and 80 % lower estimate of mortality attributable to PM2.5 for Black and Hispanic residents, respectively. Using racial/ethnic group specific CRFs did not result in a different estimation of NO2 attributable mortality for white residents, but led to âˆ¼ 50 % lower estimates of mortality for Black residents, and 290 % lower estimate for Hispanic residents. Using NO2 based on home instead of home and workplace locations results in a smaller estimate of annual mortality attributable to NO2 for all of Colorado by 2 % each year and 0.3 % for PM2.5. Our results should be interpreted as an exercise to make methodological recommendations for future health impact assessments of pollution.

Stereotactic radiosurgery for brain metastasis from cholangiocarcinoma.

OBJECTIVE: Accounting for approximately 15% of primary liver cancers and 3% of gastrointestinal malignancies, cholangiocarcinoma (CCA) poses a serious health concern given its high mortality rate. Managing brain metastases (BMs) from CCA is challenging because of their rarity and poor prognosis, with little guidance on treatment from the literature. In this study, the authors aimed to evaluate the safety and efficacy of stereotactic radiosurgery (SRS) in managing BMs from CCA. METHODS: This multicenter retrospective study included 13 CCA patients with 41 BMs treated with SRS from October 2006 to April 2022 at eight institutions affiliated with the International Radiosurgery Research Foundation. Inclusion criteria were a CCA diagnosis, an age over 18 years, no other malignancies, single-fraction SRS treatment for BMs, and at least one follow-up image. Data on demographics, tumor characteristics, treatment details, and outcomes were collected. The primary endpoints were local control (LC), intracranial progression-free survival (PFS), and overall survival (OS). The secondary endpoint was the development of adverse radiation effects (AREs). RESULTS: The median radiological follow-up was 5 months (range 1-18 months). At the last follow-up, LC was achieved in 39 (95.1%) of 41 BMs. New distant metastases were observed in 3 patients (23.1%), and the mean intracranial PFS was 9.4 months (95% CI 6.5-12.3 months). Six-month and 1-year OS rates were 38.5% and 11.5%, respectively, and the median OS was 6 months (95% CI 4.9-7.2 months). Concurrent immunotherapy was associated with a high risk of local failure (HR 29.665, 95% CI 1.799-489.206, p = 0.018), and the absence of systemic chemotherapy before SRS was linked to reduced OS (HR 6.658, 95% CI 1.173-37.776, p = 0.032). Regarding AREs, only 1 patient (7.7%) experienced right hemiparesis and was treated with corticosteroid therapy. CONCLUSIONS: SRS is an effective option for managing BMs in CCA patients, showing promise in LC and a high safety profile.

Correlation of MCP-4 and high-sensitivity C-reactive protein as a marker of inflammation in obesity and chronic periodontitis.

OBJECTIVES: Obesity is increasing in prevalence worldwide and has emerged as a strong risk factor for periodontal disease. Conversely, the remote effects of periodontal disease on various systemic diseases have been proposed. The aim of this study is to determine the presence of MCP-4 and high sensitivity C reactive protein (hsCRP) levels in gingival crevicular fluid (GCF) and serum in obese and non-obese subjects with chronic periodontitis and to find a correlation between MCP-4 and hsCRP in GCF and serum. MATERIALS AND METHODS: Forty subjects (20 males and 20 females) were selected and divided into four groups (10 subjects in each group), based on clinical parameters: group NOH (non-obese healthy), group OH (obese healthy), Group NOCP (non-obese with chronic periodontitis) and group OCP (obese with chronic periodontitis). The levels of serum and GCF MCP-4 were determined by ELISA and hsCRP levels were determined by immunoturbidimetry method. RESULTS: The mean GCF and serum concentration of MCP-4 was highest for group OCP followed by group NOCP, group OH (in GCF); group OH, group NOCP(in serum) and least in group NOH. The mean hsCRP concentration was highest for group OCP followed by group OH, group NOCP and group NOH. A significant positive correlation was found between serum and GCF MCP-4 and hsCRP levels. CONCLUSION: GCF MCP-4 concentrations increased in periodontal disease compared to health and correlated positively with the severity of disease indicating it as a novel marker of periodontal disease. The serum concentration of MCP-4 was found to be more in obese group as compared to nonobese group indicating it as a marker of obesity. Furthermore, based on the positive correlation of MCP-4 and hsCRP found in this study, it can be proposed that MCP-4 and hsCRP may be the markers linking chronic inflammation in obesity and periodontal disease.

Comparative evaluation of autologous platelet-rich fibrin and platelet-rich plasma in the treatment of mandibular degree II furcation defects: a randomized controlled clinical trial.

BACKGROUND: The treatment of molar furcation defects remains a considerable challenge in clinical practice. The identification of clinical measurements influential to treatment outcomes is critical to optimize the results of surgical periodontal therapy. The present study aimed to explore the clinical and radiographical effectiveness of autologous platelet-rich fibrin (PRF) and autologous platelet-rich plasma (PRP) in the treatment of mandibular degree II furcation defects in subjects with chronic periodontitis. MATERIAL AND METHODS: Seventy-two mandibular degree II furcation defects were treated with either autologous PRF with open flap debridement (OFD; 24 defects) or autologous PRP with OFD (25), or OFD alone (23). Clinical and radiological parameters such as probing depth, relative vertical clinical attachment level and horizontal clinical attachment level along with gingival marginal level were recorded at baseline and 9 mo postoperatively. RESULTS: All clinical and radiographic parameters showed statistically significant improvement at both the test sites (PRF with OFD and PRP with OFD) compared to those with OFD alone. Relative vertical clinical attachment level gain was also greater in PRF (2.87 ± 0.85 mm) and PRP (2.71 ± 1.04 mm) sites as compared to control site (1.37 ± 0.58 mm), and relative horizontal clinical attachment level gain was statistically significantly greater in both PRF and PRP than in the control group. CONCLUSIONS: The use of autologous PRF or PRP were both effective in the treatment of furcation defects with uneventful healing of sites.

A randomized controlled clinical trial on the clinical and microbiological efficacy of systemic satranidazole in the treatment of chronic periodontitis.

OBJECTIVE: The present clinical trial was designed to investigate the effectiveness of systemic satranidazole (SZ) as an adjunct to scaling and root planing (SRP) in the treatment of chronic periodontitis. METHODS: Sixty-six subjects presenting with at least twelve teeth with probing depth (PD) > or = 4 mm were selected. Thirty-three subjects were randomly assigned to full-mouth SRP + placebo (Group 1) and 33 subjects were assigned to full-mouth SRP + SZ (Group 2). The clinical outcomes evaluated were plaque index (PI), gingival index (GI), clinical attachment level (CAL) and PD at baseline, 1 month, 3 months and 6 months. Also, microbial analysis of dental plaque using polymerase chain reaction was done at baseline, 3 and 6 months to estimate the number of sites harboring periodontopathogens. RESULTS: Sixty subjects were evaluated up to 6 months. At 6 months, Group 2 showed greater mean reduction (3.84 +/- 1.31 mm) in PD as compared to Group 1 (1.42 +/- 1.01 mm; p < 0.05) and there was a greater mean CAL gain (3.22 +/- 1.01 mm) in Group 2 as compared to Group 1 (1.15 +/- 1.49 mm; p < 0.05). These subjects also showed significant reductions in the number of certain periodontopathogens, such as Tannerella forsythia, Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans. CONCLUSION: The systemic use of SZ, when used as an adjunct to non-surgical periodontal therapy in subjects with periodontitis, achieves significantly better clinical and microbiological results than scaling and root planing alone.

Cardiac damage following renal ischemia reperfusion injury increased with excessive consumption of high fat diet but enhanced the cardiac resistance to reperfusion stress in rat.

Renal ischemia-reperfusion (IR) injury inflicts remote cardiac dysfunction. Studies on rats fed with a high-fat diet (HD) showed contradictory results: some demonstrated increased sensitivity of the heart and kidney to IR injury, while others reported resistance. In this study, we examined cardiac dysfunction and compromised cardiac tolerance associated with renal IR in HD and standard diet (SD) fed rats. Male Wistar rats fed with HD or SD diet for 16 weeks were subjected to either renal sham or IR protocol (bilateral clamping for 45 min and reperfusion for 24 h). The hearts isolated from these rats were further subjected to normal perfusion or IR procedure to study cardiac response. Renal IR surgery negatively affected cardiac function with substantial changes in the cardiac tissues, like mitochondrial dysfunction, elevated oxidative stress, and inflammation. HD-fed rat hearts exhibited hypertrophy at the end of 16 weeks, and the consequential impact on the heart was higher in the animals underwent renal IR surgery than with sham surgery. However, the IR induction in the isolated heart from renal sham or renal IR operation showed significant tissue injury resistance and better physiological recovery in HD-fed rats. However, in SD-fed rats, only hearts from renal IR-operated rats showed resistance to cardiac IR, whereas hearts from renal sham-operated rats were more susceptible to IR damage. The augmented IR resistance in the heart with prior renal surgery was due to preserved mitochondrial bioenergetics function, reduced oxidative stress, and activation of the PI3K/AKT signaling axis.