Combined effect of G3139 and TSPO ligands on Ca(2+)-induced permeability transition in rat brain mitochondria.

Permeability of the mitochondrial outer membrane is determined by the activity of voltage-dependent anion channels (VDAC) which are regulated by many factors and proteins. One of the main partner-regulator of VDAC is the 18 kDa translocator protein (TSPO), whose role in the regulation of membrane permeability is not completely understood. We show that TSPO ligands, 1 µM PPIX and PK11195 at concentrations of 50 µM, accelerate opening of permeability transition pores (mPTP) in Ca(2+)-overloaded rat brain mitochondria (RBM). By contrast, PK11195 at 100 nM and anti-TSPO antibodies suppressed pore opening. Participation of VDAC in these processes was demonstrated by blocking VDAC with G3139, an 18-mer phosphorothioate oligonucleotides, which sensitized mitochondria to Ca(2+)-induced mPTP opening. Despite the inhibitory effect of 100 nM PK11195 and anti-TSPO antibodies alone, their combination with G3139 considerably stimulated the mPTP opening. Thus, 100 nM PK11195 and anti-TSPO antibody can modify permeability of the VDAC channel and mPTP. When VDAC channels are closed and TSPO is blocked, permeability of the VDAC for calcium seems to be the highest, which leads to accelerated pore opening.

The GnRH Antagonist Degarelix Directly Inhibits Benign Prostate Hyperplasia Cell Growth.

Gonadotropin-releasing hormone receptors (GnRHR) have been found in extrapituitary tissues, including the prostate, where they might exert a local effect on tissue growth. Degarelix is a GnRHR antagonist approved for use in patients with prostate cancer (PCa) who need androgen deprivation therapy. The slowing of prostate cell growth is a common goal shared by PCa and benign prostate hyperplasia (BPH) patients, and the effect of degarelix on BPH cells has not yet been investigated. We wanted to evaluate the direct effect of degarelix on human BPH primary cell growth. Gene expression studies performed with BPH (n=11), stage 0 (n=15), and PCa (n=65) human specimens demonstrated the presence of GNRHR1 and GNRHR2 and their respective endogenous peptide ligands. BPH-isolated epithelial and stromal cells were either cultured alone or co-cultured (1:4 or 4:1 ratio of epithelial to stromal cells) and subsequently treated with increasing concentrations of degarelix. Degarelix treatment induced a decrease in cell viability and cell proliferation rates, which occurred in parallel to an increase in apoptosis. Both epithelial and stromal BPH cells are sensitive to degarelix treatment and, interestingly, degarelix is also effective when the cells were growing in a co-culture microenvironment. In contrast to degarelix, the GnRHR agonists, leuprolide and goserelin, exerted no effect on the viability of BPH epithelial or stromal cells. In conclusion, (i) prostate tissues express GNRHR and are a potential target for degarelix; and (ii) degarelix directly inhibits BPH cell growth through a decrease in cell proliferation and an increase in apoptosis. Supporting information for this article is available online at http://www.thieme-connect.de/products.

Microwave endometrial ablation after endometrial curettage for the management of heavy menstrual bleeding.

OBJECTIVES: The aim of the present study was to evaluate the eticacy of microwave endometrial ablation after endometrial curettage, in selected patients with heavy menstrual bleeding. MATERIAL AND METHODS: Thirty-two premenopausal women with heavy menstrual bleeding underwent microwave endometrial ablation at the Department of Obstetrics and Gynecology of the University of Patras Medical School. All patients did not respond to previous medical treatment, had completed their childbearing, and did not desire future fertility. The authors chose endometrial curettage rather than hormonal pretreatment (GnRH analogs, danazol) for endometrial preparation. Posttreatment follow up protocol included physical and ultrasonographic evaluation at three, six, nine, and 12 months for the first year and yearly after. RESULTS: The authors had no cases of uterine perforation, thermal injury to adjacent organs, and infection or sepsis. During follow up, there was a gradual decrease in amenorrhea rate (90.6% - 68.8%) and in satisfaction rate (90.6% - 71.9%). Moreover during follow up, eight women underwent to total abdominal hysterectomy. Among them, seven women had uterine myomas and one woman had adenomyosis. CONCLUSIONS: Endometrial preparation with endometrial curettage seems to be a good alternative to hormonal pretreatment. It has the advantage of avoiding delays, side effects, and cost of hormonal pretreatment. Moreover, microwave endometrial ablation after endometrial curettage is successful and highly acceptable.

The Validity of the Distress Thermometer in Greek Colon Cancer Patients.

BACKGROUND: Although screening for distress is a crucial part of psycho-social care for cancer patients, there has not been a validation study for this purpose in Greece. The purpose of this study was to evaluate for the first time the psychometric properties of the Greek translation of the Distress Thermometer (DT) and Problem List (PL) in Greek colorectal cancer patients (CRC). METHODS: Participants were 84 CRC inpatients of the 1st Surgical Propedeutic Department of the Aristotle University of Thessaloniki with a mean age of 70.8±9.5 years. Participants completed the DT, PL and the Hospital Anxiety and -Depression Scale (HADS). RESULTS: The Cronbach's alpha coefficient in the DT was 0.795. Patients' mean score in the DT was 5.7±2.74, while the mean number of the reported problems in the PL was 18.85±5.50 and the mean total score of the HADS was 15.61±6.95. ROC-analysis supported that a cut-off score of 7 gives the optimal sensitivity and specificity for the DT. CONCLUSION: The index sample has manifested high levels of distress, which correspond to high need for support and improvement of the patient-provider relationship. This is probably a difficult task, since the Greek healthcare system has minimal experience of providing psycho-oncology care. The present study has indicated that the DT can be reliably used in the Greek clinical setting. Future studies, along with state provision, are essential in order to offer Greek cancer patients state-of-the-art and comprehensive care.

Post-transplantation monitoring and quantitation of microparticles in allogeneic hematopoietic cell transplantation.

BACKGROUND: Allogeneic hematopoietic stem cell transplantation (allo-HCT) represents a curative treatment for various blood-related disorders, including hematological malignancies and genetic disorders. The success of this procedure hinges on the efficacy of the conditioning regimen and the graft's ability to engraft and function properly. Microparticles (MPs), small vesicles produced from stimulated, apoptotic, or activated cells, are involved in both physiological and pathological processes. However, the impact of MPs on allo-HCT remains poorly understood. OBJECTIVES: This study aimed to investigate the presence of MPs from different cell types in grafts and patient plasma after allo-HCT, as well as their association with various parameters. We measured MPs from CD34+, CD56+, CD3+, CD19+, and CD33+ cells in grafts and patient plasma from day 0 to day 60 after transplantation. METHODS: 224 blood samples were collected from 19 consecutive allo -HCT recipients at 0, +4, +14,+30 and + 60 day as well as from their grafts. MPs isolated from the plasma and quantified by flow cytometry analysis. RESULTS: MP levels varied over time. Notably, CD34+ MP levels were linked to both early and late engraftment of neutrophils and platelets. Furthermore, grafts with high CD34+ and CD56+ MP levels in patient plasma on days 0 and + 4 were associated with late engraftment, whereas high CD33+ MP levels in both graft and patient plasma on day +4 were associated with early engraftment. Conditioning regimen affected CD19+ MP levels at day +14, and the number of CD34+, CD56+, and CD19+ MPs 30 days after transplantation was correlated with acute graft-versus-host disease. CONCLUSION: These findings suggest that MPs derived from hematopoietic cells may play a significant role in the clinical course of patients following allo-HCT.

Paediatric Anatomical Models in Radiotherapy Applications.

Anatomical models have key applications in radiotherapy, notably to help understand the relationship between radiation dose and risk of developing side effects. This review analyses whether age-specific computational phantoms, developed from healthy subjects and paediatric cancer patient data, are adequate to model a paediatric population. The phantoms used in the study were International Commission on Radiological Protection (ICRP), 4D extended cardiac torso (XCAT) and Radiotherapy Paediatric Atlas (RT-PAL), which were also compared to literature data. Organ volume data for 19 organs was collected for all phantoms and literature. ICRP was treated as the reference for comparison, and percentage difference (P.D) for the other phantoms were calculated relative to ICRP. Overall comparisons were made for each age category (1, 5, 10, 15) and each organ. Statistical analysis was performed using Microsoft Excel (version 16.59). The smallest P.D to ICRP was for Literature (-17.4%), closely followed by XCAT (26.6%). The largest was for RT-PAL (88.1%). The rectum had the largest average P.D (1,049.2%) and the large bowel had the smallest (2.0%). The P.D was 122.6% at age 1 but this decreased to 43.5% by age 15. Linear regression analysis showed a correlation between organ volume and age to be the strongest for ICRP (R2 = 0.943) and weakest for XCAT (R2 = 0.676). The phantoms are similar enough to ICRP for potential use in modelling paediatric populations. ICRP and XCAT could be used to model a healthy population, whereas RT-PAL could be used for a population undergoing/after radiotherapy.

Organic contaminants levels, distribution and risk assessment in Jeddah marine coastal zone sediments.

Herein, various organic contaminants were determined in surface sediments collected from the Jeddah coastal zone, Saudi Arabia, to assess their levels, origin and probable toxic effects on marine organisms. High hydrocarbons concentrations, indicative of an enhanced pollutant burden, were recorded in the Jeddah Lagoon (mean value 4100 mg/kg for total aliphatic hydrocarbons (∑AHC) and 5800 µg/kg for total polycyclic aromatic hydrocarbons (∑PAH)), whereas mean values in Mena Jeddah were 258 mg/kg for ∑AHC and 615 µg/kg for ∑PAH. By using molecular diagnostic ratios/indices and applying Positive Matrix Factorization, petroleum related pollution seems to predominate in Jeddah lagoons, whereas carcinogenic contaminants of pyrolytic origin were dominant in Mena Jedda. Additionally, municipal wastewaters were identified as a major source of pollution in Jeddah lagoons. Comparison of the concentrations of individual PAHs and polychlorinated biphenyls with sediment quality guidelines indicates that, despite their high total values, adverse biological effects are unlikely to occur.

Maternal in utero exposure to the endocrine disruptor di-(2-ethylhexyl) phthalate affects the blood pressure of adult male offspring.

Di-(2-ethylhexyl) phthalate (DEHP) is used industrially to add flexibility to polyvinyl chloride (PVC) polymers and is ubiquitously found in the environment, with evidence of prenatal, perinatal and early infant exposure in humans. In utero exposure to DEHP decreases circulating testosterone levels in the adult rat. In addition, DEHP reduces the expression of the angiotensin II receptors in the adrenal gland, resulting in decreased circulating aldosterone levels. The latter may have important effects on water and electrolyte balance as well as systemic arterial blood pressure. Therefore, we determined the effects of in utero exposure to DEHP on systemic arterial blood pressure in the young (2month-old) and older (6.5month-old) adult rats. Sprague-Dawley pregnant dams were exposed from gestational day 14 until birth to 300mg DEHP/kg/day. Blood pressure, heart rate, and activity data were collected using an intra-aortal transmitter in the male offspring at postnatal day (PND) 60 and PND200. A low (0.01%) and high-salt (8%) diet was used to challenge the animals at PND200. In utero exposure to DEHP resulted in reduced activity at PND60. At PND200, systolic and diastolic systemic arterial pressures as well as activity were reduced in response to DEHP exposure. This is the first evidence showing that in utero exposure to DEHP has cardiovascular and behavioral effects in the adult male offspring.

Pollution status determination using trace metals and organic contaminants of the water column in coastal areas of the Red Sea and the Gulf of Aqaba: A baseline assessment.

Herein, we aim to provide a baseline assessment of the pollution status of the water column in coastal areas of Saudi Arabia (Red Sea and the Gulf of Aqaba), using trace metals (Cd, Co, Cr, Cu, Ni, Pb and Zn), total petroleum hydrocarbons (TPHs) and polycyclic aromatic hydrocarbons (PAHs), in seawater samples obtained from 71 sampling stations in June-July 2021. Concerning trace metals, the maximum concentrations for Co, Cu and Ni were detected in Al-Shuqaiq, whereas the highest Pb and Zn concentrations were found in the Jeddah lagoon waters. Elevated concentrations of TPHs and the highest sum of PAHs were recorded in surface waters of Al Lith, Jeddah lagoon and Jeddah Mena. Overall, the concentrations of all trace metals, TPHs and individual PAHs for which environmental standards have been stipulated for the Kingdom of Saudi Arabia fall well below the threshold values.

Local and systemic autoimmune manifestations linked to hepatitis A infection.

Hepatitis A virus (HAV) represents a global burdening infectious agent causing in the majority of cases a self-limiting acute icteric syndrome, the outcome is related to the hepatic substrate and the potential pre-existing damage, whereas a plethora of extra-hepatic manifestations has also been reported. Despite the absence of post- HAV chronicity it has been associated with an additional burden on existing chronic liver diseases. Moreover, the induced immune response and the antigenic molecular mimicry are considered as triggering factors of autoimmunity with regional and distal impact. Diseases such as autoimmune hepatitis, Guillain-Barré syndrome, rheumatoid arthritis, Still's syndrome, Henoch-Schönlein purpura, autoimmune hemolytic anemia, antiphospholipid syndrome, systematic lupus erythematosus or cryoglobulinemic vasculitis have been described in patients with HAV infection. Although the exact mechanisms remain unclear, this review aims to accumulate and clarify the pathways related to this linkage.

Tritium and radiocarbon in the water column of the Red Sea.

Despite being the busiest transient sea in the world due to the Suez Canal, radionuclide distribution studies in seawater and sediment of the Red Sea remain rare. A sampling expedition in the Red Sea was conducted from June 9 to July 6, 2021, visiting a transect of several deep sampling stations located along the central axis of the basin from the Gulf of Aqaba to the southern Red Sea (near Farasan Island, Saudi Arabia). The collected seawater profile samples were analyzed for tritium, radiocarbon and oxygen-18. The observed tritium levels in surface waters of the Red Sea peaked at 0.3-0.4 TU, similar to the values observed in the western Arabian Sea (decay corrected). The values observed at waters below 150 m were around 0.2 TU, however, at depths of 450 and 750 m, tritium minima (<0.2 TU) were observed, which could be associated with a partial return flow of bottom waters from the southern to the northern Red Sea. At two stations at the depth of about 550 m, deep Δ14C minima were observed as well (-4‰ and -10‰), documenting ongoing transport of carbon in the water column, important for sink of anthropogenic carbon.

Mediterranean fever gene mutations in Greek patients with Behcet's disease.

OBJECTIVE: It is known that clinical similarities between Behcet's disease and Familial Mediterranean Fever have led to the hypothesis of a common pathogenesis. Familial Mediterranean Fever is caused by MEFV gene mutations coding for pyrin. Therefore, we examined whether these pyrin mutations are also associated with Behcet's disease. METHODS: Molecular testing for pyrin mutations was performed in 96 unrelated Greek patients with an established diagnosis of Behcets disease. The results were compared with an analysis for pyrin mutations in 140 unrelated healthy Greek controls. RESULTS: We found no pyrin mutations among the Behcet cases tested; this result is comparable with the control group. CONCLUSIONS: Pyrin gene mutations in Greek patients with Behcet's disease are not more common than those in the general population. This finding is not in agreement with the findings in other populations. It is suggested that screening for pyrin mutations not be included in the evaluation of Greeks suspected to have Behcet's disease.

Surgical management of rectal prolapse.

PURPOSE: Rectal prolapse is uncommon; however, the true incidence is unknown because of underreporting, especially in the elderly population. Full-thickness rectal prolapse, mucosal prolapse and internal prolapse are three different clinical entities, which are often combined and constitute rectal prolapse. The aim of the study is to present our experience in the surgical management of rectal prolapse. METHODS: In a 6-year period (2004-2010), 27 patients were surgically treated for rectal prolapse. The majority of patients were women (25 women, two men) and their mean age was 72.36 years. The operations performed were two Delorme's procedures, five STARR (Stapled TransAnal Rectal Resection), 14 Wells procedures, two Wells combined with Thiersch, one Altemeier, one sigmoid resection combined with Wells and two Thiersch. RESULTS: An emergency sigmoidostomy was performed on a patient after Wells operation due to obstructive ileus. One death occurred on the 5th postoperative day due to pulmonary embolism. Two recurrences observed 8 months postoperatively, one in a patient after STARR operation and one in a patient after Thiersch technique. The great majority of patients are completely relieved of symptoms. CONCLUSIONS: The application of different modalities in the treatment of rectal prolapse is attributed to the fact that cause, degree of prolapse and symptoms, vary from one patient to another. Successful approach depends on many factors, including the status of a patient's anal sphincter muscle before surgery, whether the prolapse is internal or external and the overall condition of the patient.

A retrospective analysis of 2000 cases with colorectal carcinoma.

PURPOSE: Colorectal cancer (CRC) is a major cause of death in the western world and a leading cause of cancer-related death. It is one of the most common human malignancies with >300,000 cases both in the United States and in the European Union each year. The present study was conducted to assess differences in various variables of CRC, such as location of the tumor, differentiation, Dukes classification, 5-year survival and possible changes in these patterns during the examined period. METHODS: We collected data on 2000 patients with colorectal cancer, diagnosed and treated from 1960 to 2008 in 1st Propedeutic Surgical Clinic of Aristotle's University, Thessaloniki. RESULTS: Of 2000 cases reviewed, cancer was almost equal presented to both sexes, for all groups. Rectum was the most common tumor location in all analyzed groups (40.1%). The most common tumor differentiation was the moderate one (68.5%). Concerning tumor staging, Dukes' B tumors were most common (42.5%), and the cancer-related 5-year survival was increased by the time from 42 to 71%. CONCLUSION: In the past 20 years, considerable improvements have been made in colorectal cancer therapy, and patients had received more sophisticated and multidisciplinary treatments, resulting in a better 5-year survival rate.

Rectal endometriosis: a case report.

We present the case of a 45-year-old female patient who was admitted with a history of pelvic pain, constipation, and dysmenorrhea. CT scan and u/s images revealed cholelithiasis, benign nodular hyperplasia of segment IV of the liver and uterine fibromyoma. During laparotomy, firm adhesions between the posterior wall of the uterus and the rectum were found and the incisional biopsy reveals an undifferentiated adenocarcinoma. Then, total resection of the uterus was performed with en block resection of the adherent part of the rectum and part of the posterior wall of the vagina. The final histopathological report showed the presence of uterine fibromyoma, nodular hyperplasia of the liver and rectal endometriosis without any sign of malignancy. The patient after 5 years of follow up remains healthy. Rectal endometriosis represents an uncommon localization of pelvic endometriosis where the symptoms and clinical findings are non-specific making the definitive preoperative diagnosis difficult. Endometriosis should be included in the differential diagnosis of chronic pelvic pain in combination with defecation disorders in female patients of reproductive age.

Gossypiboma presenting as mesosigmoid abscess [corrected].

INTRODUCTION: The term "gossypiboma" is used to describe any mass of non-absorbable surgical material. It is estimated that this complication appears every 1.000-10.000 procedures. It may lead to peritonitis, acute abdominal pain, intraperitoneal abscess, bowel obstruction, or perforation. REPORT OF A CASE: We present the case of an 80-year-old female patient admitted for chronic abdominal pain and fever. A CT scan and MRI were performed with a probable diagnosis of carcinoma or pelvic abscess. A surgical history of hysterectomy and repair of abdominal wall hernia with a mesh were mentioned. RESULTS: Exploratory laparotomy revealed the presence of an irregular, soft mass with characteristics of an abscess located into the mesosigmoid. Hartman's sigmoidectomy was performed, and the patient's postoperative course was uneventful. The histopathological examination confirmed the diagnosis of gossypiboma. CONCLUSIONS: Retained foreign intraperitoneal materials often represent diagnostic dilemmas, since symptomatology is no specific and the time elapsed from surgery is long. The policy of prevention's importance is highly appreciated.

Surgical management of colorectal injuries: colostomy or primary repair?

PURPOSE: Several factors have been considered important for the decision between diversion and primary repair in the surgical management of colorectal injuries. The aim of this study is to clarify whether patients with colorectal injuries need diversion or not. METHODS: From 2008 to 2010, ten patients with colorectal injuries were surgically treated by primary repair or by a staged repair. RESULTS: The patients were five men and five women, with median age 40 years (20-55). Two men and two women had rectal injuries, while 6 patients had colon injuries. The mechanism of trauma in two patients was firearm injuries, in two patients was a stab injury, in four patients was a motor vehicle accident, in one woman was iatrogenic injury during vaginal delivery, and one case was the transanal foreign body insertion. Primary repair was possible in six patients, while diversion was necessary in four patients. CONCLUSIONS: Primary repair should be attempted in the initial surgical management of all penetrating colon and intraperitoneal rectal injuries. Diversion of colonic injuries should only be considered if the colon tissue itself is inappropriate for repair due to severe edema or ischemia. The role of diversion in the management of unrepaired extraperitoneal rectal injuries and in cases with anal sphincter injuries is mandatory.

Changes in treatment of rectal cancer: increased use of low anterior resection.

PURPOSE: The most common surgical procedures for patients with rectal cancer are low anterior resection (LAR) or abdominoperineal excision (APE). The aim of the present study is to evaluate and report the changes in the incidence of LAR and APE in the surgical treatment of rectal cancer over the last 15 years in a single surgical department. METHODS: The patient sample consisted of 251 consecutive patients (mean age 65.17; age range 22-87) that underwent surgical treatment for rectal cancer in a single center from 1996 to 2010. This time frame was divided into three 5-year periods (1996-2000, 2001-2005 and 2006-2010). Patients were classified into one of the aforementioned groups, depending on the date of their treatment. RESULTS: In the first period (1996-2000), 71 patients were treated for rectal cancer. Among them, 32.4% (n = 23) underwent an abdominoperineal excision (APE) while 56.3% (n = 40) were treated with LAR. In the second period (2001-2005), included 102 patients, from which 29.4% (n = 30) received an APE and 60.8% (n = 62) underwent a LAR for their disease. In the final period (2006-2010), from the 78 patients, only 12.8% (n = 10) of them underwent APE, while 74.3% (n = 58) were treated with LAR. There was a statistically significant (chi-square test, P = 0.005) difference between the 3 periods of time concerning the performance of LAR and APE. CONCLUSIONS: According to the results of the present study, the rates of APE seem to decrease during the last 15 years, while LAR is more widely used in the surgical treatment of rectal cancer.

Inflammation of solitary caecal diverticula:a rare aetiology of acute abdominal pain [corrected].

Caecal diverticula are rare, representing the 3.6% of colonic diverticula. They may have congenital origin and remain asymptomatic, presenting as an accidental finding. We present a case of a 42-year-old Caucasian woman, admitted with a 12-h history of sudden onset of sharp right iliac fossa pain, anorexia, and nausea. There was leukocytosis (23.49 × 10(3)/µl) and increased C-reactive protein (11.76 mg/dl). CT scan showed an inflamed appendix. At laparotomy, a diffuse caecal phlegmon with an inflammatory solitary caecal diverticula was found. A limited right hemicolectomy was performed. Histological examination confirmed the caecal diverticulitis without malignancy. Post-operative period was uneventful. Three months later, endoscopy showed no diverticula or other pathologies. Solitary caecal diverticulum is very rare, but surgeons must bear this in mind in case of pain in right iliac fossa.