Cytoprotective effect of vitamin A and its clinical importance in the treatment of patients with chronic gastric ulcer

The effects of vitamin A were studied on the basal and maximal gastric secretory responses of 12 patients; and on healing in 60 patients with chronic gastric ulcer. The effect of vitamin A on ulcer healing was evaluated by a multiclinical, multicentre, randomized, prospective study in which the patients were divided into three groups. In group A the patients were treated with antacids only; in group B the patients were given antacids plus vitamin A (in doses of 3 X 50.000 U orally); and in group C the patients received antacids, vitamin A plus cyproheptadine (in doses of 3 X 4 mg orally). The treatment lasted four weeks. At the beginning and the end of treatment endoscopies were performed and ulcer sizes were measured planimetrically. Various other parameters such as ulcer index, antacid consumption and laboratory parameters were also evaluated during the four-week treatment. It was observed that: (i) vitamin A (given in doses of 100.000 U i.m.) decreased neither basal nor maximal gastric secretory responses; (ii) the number of patients with completely healed gastric ulcer was significantly higher (P less than 0.05) in groups B and C than in group A; (iii) the extent of ulcer reduction was significantly higher (P less than 0.01) in groups B and C than in group A; (iv) no significant changes were observed in ulcer index and antacid consumption during the four-week treatment in the different groups of patients; (v) the reduction of ulcer size was significantly greater (P less than 0.01) in the group treated with antacids plus vitamin A than in the group treated with antacids only, at two weeks of treatment.(ABSTRACT TRUNCATED AT 250 WORDS)     

Prognostic values of galectin-3 and the macrophage migration inhibitory factor (MIF) in human colorectal cancers.

This study aims to investigate whether the immunohistochemical levels of expression of galectin-3 and the macrophage migration inhibitory factor (MIF) are associated with prognostic values in human colorectal tumors. This was performed on 99 specimens including 69 colorectal tumors (17 Dukes A, 19 Dukes B, 15 Dukes C and 18 metastatic tumors that we labeled as D), 10 hepatic metastases from colorectal cancers and 20 normal specimens (biopsies). The immunohistochemical levels of expression of MIF and galectin-3 were quantified on routine histological slides by means of computer-assisted microscopy. Separate analyses were performed on epithelial and connective tissue. The levels of expression of both MIF and galectin-3 were very significantly higher in epithelial tumor tissue when compared with normal epithelial specimens. A positive and significant correlation between MIF and galectin-3 expression was evidenced in connective tumor tissue, and in particular in the cases associated with short survival periods (less than 5 years). In the case of the Dukes A or B tumors, we established two new prognostic groups (labeled I and II) on the basis of the levels of galectin-3 expression measured in the tumor epithelium. In the case of the Dukes C or D tumors, we established two other prognostic groups (labeled III and IV) on the basis of the levels of MIF expression measured in the connective tissue. Kaplan-Meyer analyses confirmed the additional prognostic values (as compared with conventional clinical staging) given by this new classification (groups I to IV). They show that the Dukes A or B tumors characterized by low levels of galectin-3 expression in the tumor epithelium are associated with significantly better prognoses than those characterized by high levels. In addition, the Dukes C or D tumors characterized by high levels of MIF expression in the connective tumor tissue are associated with significantly better prognoses than those characterized by low levels. In conclusions, MIF and galectin-3 expression levels in colorectal tumors are related to their levels of biological aggressiveness. These markers could be used to identify patients at risk, for whom more aggressive adjuvant therapy seems to be indicated.     

The radioprotector WR1065 reduces radiation-induced mutations at the hypoxanthine-guanine phosphoribosyl transferase locus in V79 cells

N-(2-mercaptoethyl)-lt3-diaminopropane (WR1065) protects againstradiation-induced cell killing and mutagenesis at the hypoxanthine-guaninephosphoribosyl transferase (HGPRT) locus in V79 Chinese hamsterhing fibroblast cells. At a concentration of 4 mM, WR1065 wasfound to be effective in protecting against radiation-inducedcell lethality only if present during irradiation, e.g., a dosemodification factor (DMF) of 1.9. No protective effect was observedif the protector was added within 5 min after irradiation or3 h later, e.g., DMFs of 1.0 and 1.1, respectively. The effectof WR1065 on radiation-induced mutation, expressed as resistanceto the cytotoxic purine analogue 6-thioguanine (HGPRT), wasalso investigated. In contrast to the treatment-schedule dependencefor protection by WR1065 against cell killing, this agent waseffective in reducing radiation-induced mutations regardlessof when it was administered. Following a dose of 10 Gy of ⁶⁰Co-rays, the mutation frequencies observed per 10⁶ survivors were77 ± 8, 27 ± 6, 42 ± 7, and 42 ±7 for radiation only, and WR1065 present during, immediatelyafter, or 3 h after irradiation. These data suggest that althougha segment of radiation-induced damage leading to reproductivedeath cannot be modulated through the postirradiation actionof WR1065, processes leading to the fixation of gross geneticdamage and mutation induction in surviving cells can be effectivelyaltered and interfered with leading to a marked reduction inmutation frequency.     

Retardation of cerebral dopamine turnover after morphine withdrawal and its enhanced acceleration by acute morphine administration in rats

Summary To clarify the effects of withdrawal from chronic morphine treatment on cerebral dopamine (DA) turnover, we have measured the -methyl-p-tyrosine (MT)-induced depletion of DA in five brain areas of male Wistar rats given morphine twice daily for 40 or 60 days. After the last morphine dose (50 or 70 mg/kg) the rats were withdrawn for 1, 2 or 4 days. In order to study the development of tolerance some of the rats were challenged with 10 mg/kg of morphine.Withdrawal of morphine retarded the MT-induced DA depletion in the limbic forebrain and after long enough chronic treatment in the striatum, too. The challenge dose of morphine accelerated the cerebral DA depletion slightly less in rats withdrawn for 1 day from 60-day chronic morphine treatment than in rats treated chronically with saline, but it enhanced the DA depletion more in rats withdrawn from morphine for 2 and 4 days than in chronic saline rats. This enhancement was clearest in rats withdrawn for 4 days from 60-day treatment. Thus withdrawal from morphine seems to sensitize the rats to the DA depletion accelerating effect of morphine.Our results show that repeated administration of morphine creates no marked tolerance to the DA depletion accelerating effect of morphine. In contrast, the dopaminergic neurones of the chronically treated rats seem to depend on continuous morphine administration for their normal functioning. Furthermore, the retarded DA turnover after discontinuation of morphine treatment seems to sensitize the dopaminergic neurones to the DA depletion accelerating effect of morphine. The limbic dopaminergic neurones are more easily affected by both acute and chronic morphine treatment than the striatal ones.     

Duodenal complications in necrotizing pancreatitis: Challenges of an overlooked complication

BackgroundDuodenal complications of necrotizing pancreatitis (NP) are challenging and understudied. We sought to characterize the demographics and clinical course of NP patients with duodenal complications.MethodsSingle institution retrospective review of 687 NP patients treated from 2005 to 2018.ResultsDuodenal complications developed in 40 (6%) patients including fistula in 11 (2%) and stricture in 29 (4%) patients. Patients with duodenal complications had increased computed tomography severity index (CTSI), degree of glandular necrosis, organ failure, infected necrosis, and disease duration. Mortality from NP was increased in patients with duodenal fistula (36%) compared to patients with duodenal stricture (7%) and patients without duodenal complications (9%). Surgical management of duodenal complications was required in 9/11 (82%) patients with fistula and 17/29 (59%) patients with stricture.ConclusionsDuodenal complications occurred in 6% of necrotizing pancreatitis patients. Sixty five percent of patients with duodenal complications required surgical correction. Duodenal fistula was associated with increased mortality.     

Severity of Megakaryocyte-Driven Osteosclerosis in Mpig6b-Deficient Mice Is Sex-Linked

Patients with chronic myelofibrosis often suffer from osteosclerosis, which is associated with bone pain and may lead to bone marrow failure. The pathogenesis of myelofibrosis is linked to aberrant megakaryocyte development and function. Null and loss-of-function mutations in MPIG6B, which codes for the inhibitory heparan sulfate receptor G6b-B, result in severe macrothrombocytopenia, large megakaryocyte clusters, and focal primary myelofibrosis in mice and humans. We investigated the development of osteosclerosis in Mpig6b null (Mpig6b^−/−) mice. Although male and female Mpig6b^−/− mice presented with elevated bone marrow megakaryocyte number and macrothrombocytopenia, female Mpig6b^−/− mice developed progressive splenomegaly starting at 8 weeks of age. Micro–computed tomography (μCT) of femurs showed that female Mpig6b^−/− mice had increased cortical thickness and reduced bone marrow area starting at 8 weeks of age and developed occlusion of the medullary cavity by trabeculae by 16 weeks of age. In contrast, male Mpig6b^−/− mice developed only a small number of trabeculae in the medullary cavity at the proximal diaphysis and demonstrated a temporary decrease in bone volume fraction and trabecular thickness at 16 weeks. Ovariectomy of 10-week-old female Mpig6b^−/− mice prevented the development of medullary cavity osteosclerosis, whereas orchiectomy of male Mpig6b^−/− mice did not exacerbate their disease. Importantly, ovariectomized female Mpig6b^−/− mice also demonstrated improvement in spleen weight compared to sham-operated Mpig6b^−/− mice, establishing estrogen as a contributing factor to the severity of the megakaryocyte-driven osteosclerosis. © 2021 American Society for Bone and Mineral Research (ASBMR).     

Stone extraction with loop ureteral catheter versus ureteroscopy in small distal ureteral stones—retrospective comparison of 547 consecutive patients

BackgroundTo evaluate whether stone extraction with a loop ureteral catheter (LUC) in distal ureteral stones is associated with a higher frequency of ureteral strictures compared to treatment with primary ureteroscopic stone removal (p-URS) or ureteroscopic laser lithotripsy (l-URS).MethodsFive hundred and forty-seven consecutive patients were primarily endourologically treated for distal ureteral stones in our department between 2005 and 2019 and included in the study protocol. Data was retrospectively obtained from the patients’ charts and medical reports as well as from office-based urologists. Data analysis was performed using Fisher’s exact test, Mann-Whitney test or Student’s t-test as appropriate. A level of P<0.05 was assigned statistical significance.ResultsFour hundred and twelve patients were treated by URS (p-URS n=304, l-URS n=108) and another 135 by LUC stone extraction. Median follow-up was 41 [2–159] months. There was no difference between the groups concerning age, gender, proportion of patients with ureteral stenting, operating time, hospitalization or readmission rates. The number of ureteric strictures was small in all procedures [n=3 (1.0%) in p-URS, n=2 (1.9%) in l-URS and n=2 (1.5%) in LUC] and there was no difference between the groups concerning this serious complication (p-URS vs. LUC: P=0.6465; l-URS vs. LUC: P=0.9999).ConclusionsIn small distal stones, LUC stone extraction still is an alternative to URS procedures in stone management with comparable results concerning postinterventional ureteral strictures. In experienced hands, it still has its value in accurately selected patients.     

Analyzing the learning curves of a novice and an experienced urologist for transrectal magnetic resonance imaging-ultrasound fusion prostate biopsy

BackgroundThe aim of the current study was to evaluate and compare the learning curves of transrectal magnetic resonance imaging-ultrasound fusion biopsy for two urologists with different backgrounds (Operator 1: experienced, self-trained and Operator 2: novice, trained by a mentor/MRI reading courses).MethodsA cohort of 400 patients who underwent fusion prostate biopsy in our department was analyzed. The learning curves were assessed in terms of overall and clinically significant prostate cancer (PCa) detection rates, percentage of positive biopsy cores/targeted and the percentage of PCa tissue on positive targeted cores.ResultsIncreasing trends were observed for both urologists in terms of all biopsy outcomes during the study time. For the novice urologist, a significant increase was observed for overall PCa detection rate, but not for clinically significant disease (25.44%, P=0.04/15%, P=0.145). Operator 1 showed an increasing diagnosis yield of clinically significant disease up to 104 cases. Similar cancer detection rates were observed when comparing the first and last biopsies performed by both operators. Multivariate analysis adjusted for age, PSA, prostate volume, lesion diameter and PIRADS score showed an increase of PCa detection with 51% for every 52 biopsies performed (P=0.022).ConclusionsWhen starting with magnetic resonance imaging-ultrasound fusion prostate biopsy, mentoring and prostate magnetic resonance imaging reading training allow a novice urologist to demonstrate a good initial PCa detection rate. After about 52 cases, he reached a stable PCa and clinically significant PCa detection rate, that was similar to that of an experienced urologist.     

Involvement of Fusarium spp. in fungal keratitis

Members of the filamentous fungal genus Fusarium are among the agents most frequently causing keratomycosis in humans. Fusarium keratitis is most common among agricultural workers in geographical regions with hot, humid, tropical or semi-tropical climates, but can occur more rarely in countries with temperate climates, such as Hungary. Keratitis is usually treated with a topical antifungal agent, sometimes in combination with sub-conjunctival injections and/or antimycotic agents, but therapeutic keratoplasty may be needed for patients whose corneal infection does not resolve. Early and accurate diagnosis, coupled with appropriate antifungal therapy, is crucial for improving the chances of complete recovery.     

Intracytoplasmic sperm injection in the mouse

Intracytoplasmic sperm injection (ICSI) into mouse oocytes involvesa very low survival rate. This study was designed to determinewhy ICSI frequently fails in mice. Metaphase II oocytes wereobtained from superovulated 4–6 week old F₁ hybrid mice.Spermatozoa were retrieved from the epididymis of 12–14week old F₁ hybrid mice. The spiked microinjection pipette usedto inject a spermatozoon into the ooplasm had outer and innerdiameters of 10 and 8 µm respectively. The oocytes usedin the first part of the study were not activated (group 1).Some oocytes were incubated with calcium ionophore for 5 min(group 2). The injected oocytes were evaluated 6, 20, 48 and72 h after injection. A total of 143 eggs in each group underwentICSI. In group 1, sperm heads escaped into the perivitellinespace. In all, 63 (47%) of the remaining oocytes were damagedduring the injection or had degenerated by the first evaluation.The survival rate was 53%, but fertilization did not occur.In group 2, 31 oocytes (22%) were damaged during microinjectionor soon degenerated. Two oocytes underwent accidental subzonalinsemination. Six oocytes were fertilized (4.2%) among the 78%of survivors. After injection, the sperm tail was found in thecytoplasm (27 and 31% in groups 1 and 2 respectively), the perivitellinespace (45% in both groups) or protruding through the zona pellucida(28 and 23% respectively). More oocytes degenerated when thetail remained in the cytoplasm, i.e. 78% in group 1 and 36%in group 2.