A review on PLGA particles as a sustained drug-delivery system and its effect on the retina.

In this review, the designs and recent developments of polymer-based drug delivery of Poly(lactic-co-glycolic acid) (PLGA) will be discussed for the possible treatment of age-related macular degeneration (AMD). PLGA is a versatile co-polymer that consists of synthetic lactic acid and glycolic acid monomers that are constructed to produce nanoparticles, microparticles, and scaffolds for the intraocular delivery of various drugs. As an FDA-approved polymer, PLGA has historically been well-suited for systemic slow-sustained release therapies due to its performance in biodegradability and biocompatibility. This review will examine recent in vitro and in vivo studies that provide evidence for PLGA-based particles as a therapeutic drug carrier for the treatment of AMD. Anti-angiogenic and antiproliferative effects of small peptides, small molecules, RNA molecules, and proteins within PLGA particles are briefly discussed. AMD is a leading cause of central vision loss in people over 55 years and the number of those afflicted will rise as the aging population increases. AMD has two forms that are often sequential. Dry AMD and wet AMD account for 85-90% and 10-15% of cases, respectively. The distinct categories of PLGA-based drug delivery vehicles are important for dispensing novel small molecules, RNA molecules, peptides, and proteins as a long-term effective treatment of AMD.

Using Human 'Personalized' Cybrids to Identify Drugs/Agents That Can Regulate Chronic Lymphoblastic Leukemia Mitochondrial Dysfunction.

This study uses personalized chronic lymphoblastic leukemia (CLL) cybrid cells to test various drugs/agents designed to improve mitochondrial function and cell longevity. Age-matched control (NL) and CLL cybrids were created. The NL and CLL cybrids were treated with ibrutinib (Ibr-10 µM), mitochondrial-targeted nutraceuticals such as alpha lipoic acid (ALA-1 mM), amla (Aml-300 µg), melatonin (Mel-1 mM), resveratrol (Res-100 µM) alone, or a combination of ibrutinib with nutraceuticals (Ibr + ALA, Ibr + Aml, Ibr + Mel, or Ibr + Res) for 48 h. MTT (3-(4,5-dimethylthiazolyl-2)-2,5-diphenyltetrazoliumbromide), H2DCFDA(2',7' Dichlorodihydrofluorescein diacetate), and JC1 assays were used to measure the cellular metabolism, intracellular ROS levels, and mitochondrial membrane potential (∆ψm), respectively. The expression levels of genes associated with antioxidant enzymes (SOD2, GPX3, and NOX4), apoptosis (BAX and CASP3), and inflammation (IL6, IL-1ß, TNFα, and TGFß) were measured using quantitative real-time PCR (qRT-PCR). CLL cybrids treated with Ibr + ALA, Ibr + Aml, Ibr + Mel, and Ibr + Res had (a) reduced cell survivability, (b) increased ROS production, (c) increased ∆ψm levels, (d) decreased antioxidant gene expression levels, and (e) increased apoptotic and inflammatory genes in CLL cybrids when compared with ibrutinib-alone-treated CLL cybrids. Our findings show that the addition of nutraceuticals makes the CLL cybrids more pro-apoptotic with decreased cell survival compared with CLL cybrids exposed to ibrutinib alone.

The effect of comorbidity on survival and collected CD34 + cell counts in autologous hematopoietic stem cell transplant patients.

OBJECTIVE: In this study, we aimed to report the effectiveness of hematopoietic cell transplantation-specific comorbidity index (HCT-CI) and GATMO scores in predicting overall survival (OS) who underwent autologous stem cell transplantation (ASCT). MATERIAL AND METHODS: The data of 263 MM and 204 lymphoma patients who underwent ASCT in the last 11 years were retrospectively analyzed. RESULTS: Neutrophil engraftment time, thrombocyte engraftment time and collected CD34+ cell counts were similar in MM patients with HCT-CI>2 and HCT-CI≤2 (all p>0.05). Although the estimated median OS of MM patients with HCT-CI ≤2 tended to be higher than those with HCT-CI>2, this difference was not statistically significant (52.8 vs 45 months, p=0.172). No effect of GATMO score on CD34 + count, engraftment times and OS in MM patients was detected (p>0.05). The effect of HCT-CI score on lymphoma patients was examined, it was found that the neutrophil engraftment time was longer (p=0.039) and the number of collected CD34+ cells was lower (p=0.02) in patients with HCT-CI>2 than those with HCT-CI≤2. While the estimated median OS of lymphoma patients with HCT-CI≤2 was 51.5 months, the estimated median OS of patients with HCT-CI>2 was 9.5 months (p=0.012). When lymphoma patients were divided into four groups according to their GATMO scores, the OS of the four groups was found to be different from each other (p<0.001). CONCLUSION: HCT-CI and GATMO scores predict OS in lymphoma patients but not MM patients.

MOTS-c, the Most Recent Mitochondrial Derived Peptide in Human Aging and Age-Related Diseases.

MOTS-c, a 16 amino acid mitochondrial derived peptide, is encoded from the 12S rRNA region of the mitochondrial genome. Under stress conditions, MOTS-c translocates to the nucleus where it regulates a wide range of genes in response to metabolic dysfunction. It is colocalized to mitochondria in various tissues and is found in plasma, but the levels decline with age. Since MOTS-c has important cellular functions as well as a possible hormonal role, it has been shown to have beneficial effects on age-related diseases including Diabetes, Cardiovascular diseases, Osteoporosis, postmenopausal obesity and Alzheimer. Aging is characterized by gradual loss of (mitochondrial) metabolic balance, decreased muscle homeostasis and eventual diminished physical capability, which potentially can be reversed with MOTS-c treatment. This review examines the latest findings on biological effects of MOTS-c as a nuclear regulatory peptide and focuses on the role of MOTS-c in aging and age-related disorders, including mechanisms of action and therapeutic potential.

The effect of therapeutic plasma exchange on management of HELLP Syndrome: The report of 47 patients.

BACKGROUND AND OBJECTIVES: HELLP syndrome is a life-threatening condition that may potentially cause complications during pregnancy. If not diagnosed and treated quickly, HELLP syndrome may lead to serious complications both for the mother and the baby. The aim of this study was to determin the effectiveness of therapeutic plasma exchange (TPE) for treatment of Class-I HELLP syndrome. MATERIALS AND METHODS: Laboratory results from 47 patients with Class-I HELLP syndrome patients who underwent TPE between 2011 and 2020 were recorded before and after the procedure. A central venous catheter was inserted, and TPE was performed in patients who had not responded to delivery, steroid, and supportive therapy (blood products, anti-hypertensive therapy, intravenous fluid administration, and antibiotics) within 24 hours after the diagnosis of Class I HELLP syndrome according to the Mississippi Criteria. RESULTS: The average age of patients was 33 ± 4.7 years (range; 21-39 years). A mean of 5 (range; 4 to 6) TPE sessions were performed. There was a statistically significant decrease in total bilirubin, lactic dehydrogenase, aspartate aminotransferase, and alanine aminotransferase levels in all patients, whereas a significant increase in platelet count was observed (p < 0.05). Furthermore, clinical and laboratory improvement was achieved. CONCLUSION: In all patients with HELLP syndrome, a dramatically clinical and laboratory improvement occurred after TPE. Our study suggests that postpartum use of TPE within 24 hours is an efficient treatment option for Class-I HELLP syndrome.

Selection of the mobilization regimen in lymphoma patients: A retrospective cohort study.

BACKGROUND AND OBJECTIVES: Consolidation with autologous stem cell transplantation (ASCT) is recommended for patients with recurrent or refractory lymphoma after salvage chemotherapy. Stem cells which will be used in ASCT are provided by mobilization using granulocyte colony stimulation factor (G-CSF) or chemotherapy plus G-CSF. The aim of this study was to compare the effect of various mobilization regimens on the clinical parameters of lymphoma patients. MATERIALS AND METHODS: Mobilization interventions of lymphoma patients were analysed retrospectively. The patients were divided into 3 groups according to the mobilization method implemented to collect stem cells before ASCT, (Group 1: Salvage chemotherapy plus G-CSF, Group 2: Cyclophosphamide plus G-CSF, Group 3: G-CSF alone). RESULTS: Analysis of CD34+ cell counts of the 3 groups revealed a significant difference (p < 0.001). Although the number of CD34+ cells collected were different, the neutrophil and platelet engraftment of the 3 groups were similar (p > 0.05). Furthermore, the results were similar in the separate analysis of NHL and HL patients. While the mobilization success rate in group 1 was 97.8 %, it was 90.2 % in group 3. This difference showed a certain trend towards statistical significance (p = 0.074). Patients who received DHAP plus G-CSF had a higher CD34+ count, while neutrophil engraftment was shorter than with ESHAP plus G-CSF (p < 0.05). CONCLUSION: Although the success rate of mobilization and number of CD34+ cell collected were higher in the salvage chemotherapy plus G-CSF than G-CSF alone, G-CSF alone group provided similar neutrophil and thrombocyte engraftment in most lymphoma patients.

An innovation in stem cell harvesting: Heparin use.

BACKGROUND AND OBJECTIVES: Stem cell transplantation is a growing treatment strategy for most malignant and non- malignant hematological diseases. Plerixafor and granulocyte colony stimulating factor (G-CSF) are usually used in mobilization regimens to increase the CD34+ cell count in the harvest. Heparin is a sulphated glycosaminoglycated polymer with 12-15 kDa mass. Heparin inhibits the CXCR4/SDF1 axis, as does plerixafor. In this study, our aim was to investigate the effect of using heparin on stem cell mobilization and harvesting. MATERIALS AND METHODS: We administered 5000 units of unfractioned heparin intravenously in 150 mL (mL) of isotonic sodium chloride solution, 15 min before the stem cell harvesting procedure to 141 patients who underwent bone marrow transplantation between the years of 2018 and 2019 at our Stem Cell Transplantation Unit. Thirty patients were included as a control group, and they were not given heparin. The study population included patients with multiple myeloma and lymphoma equally in each group. RESULTS: In all patients hematopoeitic stem cells were successfully harvested in a single cycle of apheresis. In multiple myeloma patients who received heparin, the mean collected CD34+ cell number was 8 × 106/kg, and the mean CD34+ cell number yield was 12,555/µl. In the control group, the mean collected CD34+ cell number was 4,2 × 106/kg, and mean CD34+ cell number in yield was 492/µl. In lymphoma patients who received heparin, the mean collected CD34+ cell number was 6,8 × 106/kg, and the mean CD34+ cell number was 1421/µl. In the control group the mean collected CD34+ cell number was 4,3 × 106/kg, and the mean CD34+ cell number was 358/µl. The effect of heparin on the collected stem cell number in both myeloma and lymphoma patients was statistically significant (p < 0.01). CONCLUSIONS: Our results have shown that heparin increases harvested stem cell numbers significantly. Heparin may be a promising agent for stem cell harvesting.

Therapeutic plasma exchange for envenomation: Is it reasonable?

BACKGROUND AND OBJECTIVES: The incidence of poisoning due to snakebite and Crimean Congo Hemorrhagic Fever (CCHF), referred to as 'envenomation', varies according to the region, and many deaths occur every year. Therapeutic plasma exchange (TPE) is a method of extracorporeal blood purification that clears toxins and virus load from the circulation. Therefore, its use has been increasing recently in envenomation cases. However, there are a limited number of studies on poisoning due to snakebite and CCHF. In the present study, we share our TPE experience retrospectively in patients diagnosed with poisoning due to snakebite and CCHF between 2010 and 2019. MATERIALS AND METHODS: A total of 26 patiens, including 20 patients with poisoning due to snakebite and 6 CCHF patients were treated with TPE. Demographic data, clinical status, and outcomes of patients were recorded. Routine biochemical and hematologic laboratory parameters were analyzed before and after TPE. TPE was performed by using centrifugation technology via a central venous catheter. Fresh frozen plasma was used as replacement fluid. RESULTS: An average of 3.95 (1-11) apheresis sessions were applied to patients poisoned due to snakebite, and 19 patients (95 %) were discharged in an average of 8.3 (1-17) days without any complications. None of the patients enrolled in the study lost their limbs. Only one patient died due to disseminated intravascular coagulopathy. Six patients with CCHF who received 5 sessions of TPE on average were discharged successfully after an average of 6.5 days. No adverse events or complications were observed in any patient after TPE. CONCLUSIONS: TPE is a good alternative and a reliable method in treating envenomation cases who are refractory to supportive measures. TPE should be performed without delay in cases of poisoning due to snakebite and CCHF.

Filgrastim alone versus cyclophosphamide and filgrastim for mobilization in multiple myeloma patients.

BACKGROUND AND OBJECTIVE: High-dose chemotherapy followed by autologous stem cell transplantation (ASCT) is standard treatment approach in most multiple myeloma (MM) patients. Before ASCT, chemomobilization or only granulocyte-colony stimulating factor (G-CSF) mobilization can be preferred in stem cell mobilization. The primary aim of the study is to compare the effect of the two mobilization regimens on hematopoietic engraftment times, CD34+cell counts and number of apheresis required to harvest stem cells. MATERIALS AND METHODS: The records of MM patients who applied to our hospital between 2010 and 2020 were analysed retrospectively. Patients were divided into two groups (Group A: Cyclophosphamide plus filgrastim, Group B: Filgrastim alone) according to the mobilization regimen. RESULTS: A total of 223 MM patients were included in this study (Group A:153, Group B:70 patients). When the patients in Group A and Group B were compared, the number of collected CD34+ cells were higher in Group A (p < 0.001). However, there was no significant difference between the two groups in terms of median times to neutrophil and platelet engraftment, and number of apheresis required to harvest stem cells (p > 0.05). The rate of infection development during mobilization in the patients in group A and the duration of hospitalization of these patients were higher than the patients in group B (p < 0.001). Patients receiving >6 cycles of chemotherapy and immunomodulatory treatment had lower collected CD34+ cells than other patients (p = 0.012 and p = 0.054). CONCLUSION: Based on our findings, filgrastim alone seems to provide a sufficient amount of stem cells in MM patients.

Lenograstim versus filgrastim in mobilization before autologous hematopoietic stem cell transplantation in patients with multiple myeloma and lymphoma - Single center experience.

OBJECTIVE: Peripheral blood stem cell transplantation is frequently used in the treatment of various hematological malignancies after intensive chemotherapy. The primary aim of our study is to compare the amount of collected CD34+ cells and engraftment times in patients mobilized with filgrastim or lenograstim. MATERIAL AND METHODS: Demographic and clinical data of multiple myeloma (MM) and lymphoma patients who underwent autologous transplantation and mobilized with G-CSF (filgrastim or lenograstim) without chemotherapy were collected retrospectively. RESULTS: One hundred eleven MM and 58 lymphoma patients were included in the study. When mobilization with filgrastim and lenograstim was compared in MM patients, there was no significant difference in neutrophil and thrombocyte engraftment times of lenograstim and filgrastim groups (p = 0.931 p = 0.135, respectively). Similarly, the median number of CD34+ cells collected in patients receiving filgrastim and lenograstim was very similar (4.2 × 106/kg vs 4.3 × 106/kg, p = 0.977). When compared with patients who received lenalidomide before transplantation and patients who did not receive lenalidomide, the CD34+ counts of the two groups were similar. However, neutrophil and platelet engraftment times in the group not receiving lenalidomide tended to be shorter (p = 0.095 and p = 0.12, respectively). When lymphoma patients mobilized with filgrastim and lenograstim were compared, neutrophil engraftment time (p = 0.498), thrombocyte engraftment time (p = 0.184), collected CD34+ cell counts (p = 0.179) and mobilization success (p = 0.161) of the groups mobilized with filgrastim and lenograstim were similar. CONCLUSION: The superiority of the two agents to each other could not be demonstrated. Multi-center prospective studies with larger numbers of patients are needed.

Life-saving effect of convalescent plasma treatment in covid-19 disease: Clinical trial from eastern Anatolia.

AIM: Convalescent Plasma (CP) therapy is of interest as no vaccine or specific treatment is available for emerging viruses such as severe acute respiratory syndrome coronavirus 2 causing Covid-19. It was aimed to report the results of our patients who underwent CP in the treatment of Covid-19. METHODS: CP treatment was applied to 26 Covid-19 patients in intensive care unit who had quantitative reverse transcriptase-polymerase chain reaction positive Sars-Cov-2 infection. Plasma was collected at least 14 days after complete recovery from patients who had mild or moderate infection with Sars-Cov-2 infection. The collected CP (200cc) were applied to severe Covid-19 patients. Laboratory values of patients just before CP and after 7 days were compared. RESULTS: There were no statistically significant differences in leukocyte, neutrophil, lymphocyte, platelet, CRP, ferritin, LDH, ALT, AST, sO2 and total bilirubin values just before and after 1 week of CP. A statistically significant difference was found between age and lymphocyte values of living and dying patients. The patients who died were determined to have older age (74,6 vs 61,85, p = 0,018) and more severe lymphopenia (0,47 vs 1,18, p = 0,001). CONCLUSION: CP therapy has the potential to provide immediate and promising treatment options before specific vaccines and treatments are developed. In early stage Covid-19 patients who do not need mechanical ventilation, CP treatment may be a curative treatment option.

DHAP plus filgrastim as an effective peripheral stem cell mobilization regimen for autologous stem-cell transplantation in patients with relapsed/refractory lymphoma: A single center experience.

This study aimed to evaluate the efficiency of DHAP regimen plus filgrastim for mobilization of stem cells in patients with recurrent and/or refractory lymphoma. Thirty-four patients who took DHAP as salvage therapy prior to autologous stem cell transplantation were included. After chemotherapies, 2 cycles of DHAP plus filgrastim were administered to the patients. Stem cells from 32 patients (94%) were collected on median 11th day (8-12), and the median collected CD34(+) cell dose was 9.7 × 10(6)/kg (range 3.8-41.6). DHAP plus filgrastim was found to be an effective chemotherapy regimen in mobilizing CD34(+) stem cells into the peripheral.

Leukapheresis treatment in elderly acute leukemia patients with hyperleukocytosis: A single center experience.

AIM: Leukapheresis is an invasive treatment modality used for hyperleukocytosis. Various drugs and fluids are used during the leukapheresis. Aging itself and associated factors such as increased comorbidity, decreased tolerance to drugs, increased drug toxicity give rise to the application of other treatment modalities in elderly patients. Treatment of acute leukemia in the elderly differs from young patients. Consequently, we assumed that outcome, effectiveness, and side effects of leukapheresis treatment used for acute leukemia patients with hyperleukocytosis may be different in elderly compared to younger patients. METHODS: We retrospectively evaluated a total of 39 patients. Eighteen patients were 65 years and older. Indications for leukapheresis were determined as symptoms of leukostasis and prophylaxis. Acid citrate dextrose-A, calcium gluconate, and plasma were used during the leukapheresis. Age, sex, diagnosis, count, and indications of leukapheresis procedures, leukocyte count, and lactate dehydrogenase level were analyzed at the onset of and after leukapheresis; side effects, causes of death, early and total mortality rates were also analyzed. We compared the two groups with regard to effectiveness, clinical outcomes, and side effects. RESULTS: There were no statistically significant differences between the two groups with respect to sex, diagnosis, initial leukocyte count, lactate dehydrogenase level, number of leukapheresis procedures, rates of side effects, or early and total mortality (P > 0.05). Leukapheresis treatment was effective in both groups (P < 0.05) and no significant difference was found in its effectiveness between two groups (P > 0.05). CONCLUSION: Leukapheresis is an effective and safe treatment modality in elderly acute leukemia patients with hyperleukocytosis.

Leukapheresis in acute myeloid leukemia patients with hyperleukocytosis: A single center experience.

Hyperleukocytosis is defined as WBC count above 100,000/mm(3) in peripheral blood. Increased WBC count leads to leukocyte aggregation, increased blood viscosity, and consequently results in stasis in small blood vessels. Ultimate neurological, pulmonary, gastrointestinal complications, coagulopathy, and tumor lysis syndrome cause increase in morbidity and mortality. Leukapheresis is a treatment modality used for hyperleukocytosis. In patients presenting with hyperleukocytosis the indications for leukapheresis were accepted as having symptoms of leukostasis and prophylactic. Indications for leukapheresis in prophylactic group evaluated according to WBC count. We report a single center experience about leukapheresis in managing 31 AML patients with hyperleukocytosis. In addition to demographic characteristics, disease-related clinical and laboratory findings of the patients were recorded. Survival rates were also calculated. Ten patients were female. The most common of AML subtype was AML-M2. The median number of leukapheresis per patient was 2 and totally 60 leukapheresis cycles were performed in all patients. There was a significant decrease in WBC count and LDH level after leukapheresis as compared with the baseline values (p < 0.05). Early and total mortality were 16.1% and 58.0%, respectively. Alive and died patients were evaluated according to baseline WBC, LDH; increased WBC count and LDH level were found in died patients (p < 0.05). According to leukapheresis indications, patients were divided into two groups: 14 patients in symptomatic leukostasis, 17 patients in prophylaxis. No statistically significant differences were noted between both groups in leukapheresis effectiveness, mean survival time, early and total mortality rate (p > 0.05). None of our patients suffered serious side effects and tumor lysis syndrome during or after apheresis. Leukapheresis is an effective and safe approach to reduce WBC counts in patients with AML with hyperleukocytosis. Further evidence-based data obtained from larger sample sizes are required to better understand the impact of prophylaxis leukapheresis on early and total mortality of AML patients with hyperleukocytosis.

A life-saving therapy in Class I HELLP syndrome: Therapeutic plasma exchange.

HELLP syndrome, which can affect multiple organ systems and cause maternal and fetal mortality, is a serious complication of pregnancy characterized by microangiopathic hemolytic anemia, elevation of liver enzymes, and thrombocytopenia. Delivering the infant usually suffices for the treatment of this syndrome. In cases with Class I HELLP syndrome, however, the clinical picture may rapidly deteriorate despite delivery. In this paper we presented the outcomes with the use of therapeutic plasma exchange in cases with class I HELLP syndrome. This study included 21 patients diagnosed with the Class I HELLP syndrome at Inonu University Faculty of Medicine, Department of Hematology between 2011 and 2014. A central venous catheter was placed and plasma exchange therapy was begun in patients unresponsive to delivery, steroid, and supportive therapy (blood and blood products, antihypertensive therapy, intravenous fluid administration, and antibiotics) within 24 hours after the diagnosis of Class I HELLP syndrome according to the Mississippi Criteria. All patients underwent therapeutic plasma exchange for three sessions each with a 1:1 volume. Hemogram and biochemical parameters of the patients were evaluated before and after the procedure. According to results, there was a statistically significant decrease in total bilirubin, LDH, AST, and ALT levels whereas a significant increase in platelet count was observed. Hemoglobin levels were increased, although this increase was not statistically significant. HELLP syndrome is primarily treated with the delivery of infant; however, some cases may show disease progression despite completion of delivery. As a potential cause of both maternal and fetal mortality, HELLP syndrome condition should be aggressively treated. Therapeutic plasma exchange is one of the available treatment options. Our study has found that postpartum use of plasma exchange therapy within 24 hours is an efficient and lifesaving treatment choice in Class I HELLP syndrome.

Therapeutic plasma-exchange in hematologic disease: results from a single center in Eastern Anatolia.

Therapeutic plasma-exchange (TPE) is used as primary and adjunctive therapy in treatment of several hematologic diseases. We retrospectively evaluated the results of TPE in hematologic diseases during 2008-2012. A total of 301 TPE procedures were performed in 44 patients (19 male and 25 female, with mean age of 50.6±15years). Fifteen of 44 patients had thrombotic thrombocytopenic purpura (TTP), 14 patients had HELLP syndrome (Hemolysis Elevated Liver enzymes, Low Platelet count), 10 patients had multiple myeloma-hyperviscosity and the rest five patients had snake bite. Fresh frozen plasma (FFP) was used as replacement fluid. Complete response (CR) was achieved on 13 patients (87%) in primarily TTP. CR was achieved in all other three diseases. Total complications were detected in 8.1% of the TPE procedures. Adverse events (AEs), were seen in 5.4% of all procedures. None of the patients died from any complication. AE occurred in 4% (Grade-I), 1% (Grade-II), and 0.3% (Grade-III) of the procedures. The most common AE were nausea/vomiting, hypotension, pruritus and abdominal pain. TPE is effectively and safely carried out in our center in hematologic diseases.

Exploring the Gender-Specific Impact of Intraperitoneal Bupivacaine on Early Postoperative Pain in Sleeve Gastrectomy.

Background: Early postoperative pain is a significant problem in bariatric and metabolic surgery. Our study aimed to investigate the potential role of intraperitoneal bupivacaine hydrochloride in pain management in the early postoperative period after bariatric and metabolic surgery. Methods: This double-blind, prospective, randomized, controlled study included 68 individuals who underwent bariatric and metabolic surgery at the Department of Surgery, Istanbul Aydin University Hospital. The study group received 20 mL of 0.5% bupivacaine hydrochloride intraperitoneally at the operative site, and the control group received 20 mL of normal saline. Visual analog scale (VAS) scores of each patient were recorded at 2nd, 4th, and 6th hours postoperatively. Results: Our study found significant differences in VAS scores of patients between study group and control group at 2nd, 4th, and 6th hours postoperatively. Significant differences were found between male and female patients in the control group at 2nd, 4th, and 6th hours postoperatively. Interestingly, no significant difference was found between female patients in the study group and control group at 2nd, 4th, and 6th hours postoperatively. Conclusions: Our study suggests that intraperitoneal administration of bupivacaine hydrochloride is effective in reducing early postoperative pain in male patients. However, no significant difference was found between the study group and the control group in female patients. Our results indicate that there may be a gender-related difference in the response to bupivacaine administration. Further research is needed to confirm these findings and determine the optimal dosing and administration of local anesthetics for postoperative pain management.

Stability Determination of Intact Humanin-G with Characterizations of Oxidation and Dimerization Patterns.

Humanin is the first identified mitochondrial-derived peptide. Humanin-G (HNG) is a variant of Humanin that has significantly higher cytoprotective properties. Here, we describe the stability features of HNG in different conditions and characterize HNG degradation, oxidation, and dimerization patterns over short-term and long-term periods. HNG solutions were prepared in high-performance liquid chromatography (HPLC) water or MO formulation and stored at either 4 °C or 37 °C. Stored HNG samples were analyzed using HPLC and high-resolution mass spectrometry (HRMS). Using HPLC, full-length HNG peptides in HPLC water decreased significantly with time and higher temperature, while HNG in MO formulation remained stable up to 95% at 4 °C on day 28. HNG peptides in HPLC water, phosphate-buffered saline (PBS) and MO formulation were incubated at 37 °C and analyzed at day 1, day 7 and day 14 using HRMS. Concentrations of full-length HNG peptide in HPLC water and PBS declined over time with a corresponding appearance of new peaks that increased over time. These new peaks were identified to be singly oxidized HNG, doubly oxidized HNG, homodimerized HNG, singly oxidized homodimerized HNG, and doubly oxidized homodimerized HNG. Our results may help researchers improve the experimental design to further understand the critical role of HNG in human diseases.

Predictors of atrial arrhythmias in patients with mitral valve prolapse.

OBJECTIVE: Arrhythmias have been reported to occur frequently in symptomatic patients with mitral valve prolapse (MVP). The mechanisms causing atrial arrhythmias in patients with MVP have not been fully investigated. The purpose of this study was to determine the clinical, echocardiographic and heart rate variability parameters, and plasma concentrations of electrolytes and inflammatory markers in predicting atrial arrhythmias in patients with MVP. METHODS: A total of 58 consecutive patients with MVP were included in this study. We performed electrocardiography, echocardiography, Holter analysis, routine biochemical tests including plasma concentrations of electrolytes and inflammatory markers, and evaluated the clinical characteristics. Atrial arrhythmia was defined as occurrence of any of the following: atrial premature contractions, atrial couplets, supraventricular tachycardia, atrial flutter or fibrillation documented by Holter analysis, continuous monitoring or by electrocardiography. RESULTS: Twenty-eight patients (48%) had atrial arrhythmias, and 30 (52%) patients had no atrial arrhythmias. Univariable predictors of atrial arrhythmias included isovolumetric relaxation time, lateral systolic (S'), lateral late diastolic (A'), septal A' Doppler velocities, anterior mitral leaflet thickness, anterior mitral leaflet thickness of > or =5 mm, posterior mitral leaflet thickness and the occurrence of moderate to severe mitral regurgitation. Multivariable logistic regression analysis showed that occurrence of moderate to severe mitral regurgitation was the only independent predictor of atrial arrhythmias (relative risk: 2.4, 95% confidence interval 1.32-4.86, P = 0.005). CONCLUSIONS: The present study showed that the only independent predictor of atrial arrhythmias in patients with MVP is the occurrence of moderate to severe mitral regurgitation.

Mitral valve replacement impairs the flow in the left atrial appendage in mitral regurgitation.

OBJECTIVE: We aimed to assess the left atrial appendage (LAA) flow velocities of rheumatic valves in 46 patients, diagnosed with isolated mitral regurgitation (MR) (16 patients), mitral stenosis (MS) (14 patients) and combined MS and MR (MS + MR) (16 patients) before and after operation. METHODS: The patients were subdivided into two groups, according to rhythm: sinus (SR) (20 patients) and atrial fibrillation (AF) (26 patients). All patients underwent transthoracic and transoesophageal echocardiography before and after the operation. RESULTS: Preoperatively LAA flow velocities were the best in the MR group among the three groups. Postoperatively there was no statistically significant difference between the MR group and the other two groups for mean peak emptying and filling velocities in patients with SR and AF. The incidence of spontaneous echo contrast (SEC) and thrombus significantly increased in the MR group after operation. Thrombus was only seen in patients with AF at the postoperative period. CONCLUSIONS: Mitral valve replacement disturbs LAA flow velocities and increases the risk of thrombus formation in patients with MR. This risk was more obvious in cases with AF. Impaired left atrial appendage flow velocities increase the risk of thrombus formation. We recommend close follow-up for the increased possibility of thrombus formation in patients who had MR preoperatively and AF postoperatively.