Retrospective Study of the Use of Heparins in Pregnant Women and in vitro Testing on the HCT 116 Colorectal Carcinoma Cell Line.

Introduction: Pregnant women manifest an increased risk of developing coagulation disorders. Unfractionated heparin (HEP) and low-molecular-weight heparin (LMWHep) are considered as selective medication in the case of pregnancy which needs anticoagulant treatment. In addition to anticoagulant properties, HEP and its derivatives manifest other properties including anti-cancer potential. According to Globocan's latest data, colorectal cancer (CRC) is the second most encountered form of malignancy in the case of women, manifesting some special particularities, as confusion of symptoms from cancer with symptoms encountered normally in pregnant women (such as constipation or rectal bleeding), delayed diagnosis because of limitations imposed both for the fetus and for the mother, and the need for special treatment. Aim: The aim of the present work is to follow the incidence and safety of consumption of HEP and LMWHep in the case of pregnant women and to analyze their potential on the HCT 116 colorectal carcinoma cells. Results: Analyzing the consumption of heparins in case of pregnant women hospitalized from 01.01.2022 to 31.12.2022 at the Pius Brînzeu" Emergency Clinical Hospital from Timisoara, Obstetrics and Gynecology Clinic I, it was observed that 44,6% of the patients were administered the following medication and no administration risks were observed. When tested on HCT 116 cells, heparins manifested a significant anti-migratory effect (with wound healing rates of 2,6%, when tested with HEP 100 UI concentration and 14.52% wound healing rates in case of fraxiparine 100 UI). In addition, different signs of apoptosis were observed, suggesting the pro-apoptotic potential of the tested substances. Conclusions: Heparins remain the preferred medication to be administered to pregnant women with the potential for coagulation disorders, showing a high safety profile. Testing on the cancerous line of colorectal carcinoma highlights important properties that stimulate future studies, to establish the anti-tumor potential and the exact mechanism of action.

Analysis of the Level of Adiponectin and Selected Cytokines in Patients with Knee Osteoarthritis.

Background and Objectives: Knee osteoarthritis (KOA) is a degenerative disease that is continuously targeting people of different ages, but especially the elderly population, the number of which tends to increase continuously at the global level. Apart from age, excess weight can influence the evolution of the disease, with obesity being associated with a weak inflammation stage and an imbalance between pro-inflammatory and anti-inflammatory cytokines. The present work aimed to analyze specific biomarkers, namely ACRP-30, IL-10, TNF-α, and IL-6, in knee synovial fluid, and correlate them with KOA patients' clinical data, radiographic changes, and functional and pain scores. Materials and Methods: 24 subjects with KOA and over 50 years of age participate in the present study. Synovial fluid was harvested using ultrasound guidance from the target knees of the enrolled KOA patients, and the levels of ACRP-30, IL-10, TNF-α, and IL-6 were measured using enzyme-linked immunosorbent assays (ELISA). All patients underwent a supine X-ray at the target knee and were classified using Kellgren-Lawrence (K-L) grading. The Western Ontario and McMaster University Osteoarthritis Index (WOMAC) was used to assess self-reported physical function, pain, and stiffness. Results: The obtained results highlighted a significant correlation between age and adiponectin level (p = 0.0451, r = -0.412). Also, the IL-10 values are lower in cases where the intensity of the pain is more pronounced (p = 0.0405, r = -0.421). In addition, analyzing the data by gender, it was observed that in the case of males, stiffness is more related to age (p = 0.0079, r = 0.7993), compared to women (p = 0.0203, r = 0.6223). In the case of women, the progression of the disease tends to increase more intensively the WOMAC score's total values (p = 0.00031, r = 0.8342), compared with men (p = 0.0289, r = 7013). Regarding interleukins and BMI, significant correlations were observed only in the case of men. Conclusions: A significant correlation between age and adiponectin, and adiponectin and IL-6, suggests that advanced age may contribute to adiponectin reduction. Comparing men with women, it was observed that men's age is more related to rigidity, and IL-6 and IL-10 are directly correlated to BMI; in addition, women seem to be more sensitive to pain and stiffness.

Recovery of Spinal Walking in Paraplegic Dogs Using Physiotherapy and Supportive Devices to Maintain the Standing Position.

Paraplegic patients have always been ideal candidates for physiotherapy due to their body's inability to recover on its own. Regardless of the cause that led to the onset of paraplegia (traumatic or degenerative), physiotherapy helps these patients with devices and methods designed to restore the proper functioning of their motility, as well as their quality of life. A total of 60 paraplegic dogs without deep pain in the hindlimbs caused by intervertebral disc extrusion or thoracolumbar fractures underwent physiotherapy sessions: manual therapy (massage), electrostimulation (10-20 min with possible repetition on the same day), ultrasound therapy, laser therapy, hydrotherapy, and assisted gait in supportive devices or on treadmills to stimulate and relearn walking, which was the main focus of the study. To maintain the standing position over time, we developed different devices adapted for each patient depending on the degree of damage and the possible associated pathologies: harnesses, trolleys, straps, exercise rollers, balancing platforms and mattresses, physio balls and rollers for recovery of proprioception. The main objective of our study was to demonstrate that physiotherapy and assisted gait in supportive devices to maintain the standing position may help paraplegic dogs to develop spinal walking. Concurrent pathologies (skin wounds, urinary infections, etc.) were managed concomitantly. Recovery of SW was evaluated by progression in regaining the reflectivity, nociception, gait score, and quality of life. After 125 to 320 physiotherapy sessions (25 to 64 weeks), 35 dogs (58.33%) developed spinal walking and were able to walk without falling or falling only sometimes in the case of a quick look (gait score 11.6 ± 1.57, with 14 considered normal), with a lack of coordination between the thoracic and pelvic limbs or difficulties in turning, especially when changing direction, but with the recovery of the quadrupedal position in less than 30 s. The majority of dogs recovering SW were of small size, with a median weight of 6.83 kg (range: 1.5-15.7), mixed breed (n = 9; 25.71%), Teckel (n = 4; 11.43%), Bichon (n = 5; 14.28%), Pekingese (n = 4; 11.43%), and Caniche (n = 2; 5.71%), while those who did not recover SW were larger in size, 15.59 kg (range: 5.5-45.2), and mixed breed (n = 16; 64%).

A Case Study of Photosensitivity Associated with Anaplasma spp. Infection in Cattle.

Anaplasma infection has not previously been reported as a cause of photosensitization. This case presents a five-year-old Holstein cow in her fifth month of gestation with skin injury of nonpigmented areas clearly delimited from adjacent unaffected pigmented skin. Specific lesions included alopecia, localized oedema, desquamation erythema, serous exudation, thick detached skin, fissures, crusting, and necrosis, indicating photodermatitis. Hematological abnormalities were leukocytosis with neutrophilia and normocytic hypochromic anemia. Based on a hemoparasitic examination of blood smears, the organism Anaplasma spp. was observed within the red blood cells. Biochemical analyses revealed increased serum liver enzyme activity associated with hepatocellular damage and cholestasis. This cow was RT-PCR positive for Anaplasma spp. infection. After treatment with oxytetracycline started, its condition improved within 24 h, and it recovered completely within 30 days. In this case, the underlying pathogenic mechanism of Anaplasma spp. infection facilitated the impairment of bile flow and liver function, resulting in hepatogenous photosensitization.

The safety profile of new antidiabetic xanthine derivatives and their chitosan based formulations.

The safety profile of new antidiabetic xanthine derivatives with thiazolidine­4­one scaffold (6, 7) and their new chitosan based formulations (CS-6, CS-7), administrated to diabetic rats, have been evaluated in terms of biochemical markers of liver and kidney function as well as of hematological markers. The effect on lipid profile and clinic parameters (body weight, food and water intake) has been also evaluated. The treatment of diabetic rats with xanthine derivatives (6, 7) and chitosan based formulations (CS-6, CS-7) was associated with lower liver enzymes (AST, ALT, LDH) and bilirubin (direct, total) values compared to the non-treated diabetic rats, that means the tested derivatives/formulations have improved the liver function injured in diabetes mellitus conditions. Also the kidney biochemical markers (creatinine, uric acid, urea) were significantly decreased in diabetic rats treated with 6, 7 and chitosan microparticles (CS-6, CS-7). The values of biochemical markers of liver and kidney functions were even better than the values recorded for pioglitazone, used as standard antidiabetic drug. The improving effect on kidney function was proved by the histopathological study. Moreover, the xanthine derivatives and their chitosan based formulation were associated with improved hematological markers compared to the non-treated diabetic rats which mean the improving of the hemorheological state. These results support the safety profile of new xanthine derivatives with thiazolidine­4­one scaffold (6, 7) and their new chitosan based formulations (CS-6, CS-7) and their potential applications for the treatment of diabetes mellitus syndrome.

Ki-67 and p53 expression of the fallopian tube mucosa in breast cancer patients with hereditary risk.

PURPOSE: The fallopian tube has been implicated as a site of origin of sporadic and BRCA1-related ovarian cancer. To investigate if Ki-67 or p53 is altered in BRCA1 mutation carriers, we have studied the expression of these markers in morphologically normal mucosa in the fallopian tube and fimbriae. METHODS: Prophylactic adnexectomy specimens from 24 patients (eight BRCA1 mutation carriers, eight non-mutation carriers, and eight with unknown BRCA1 status), were scored by automated image analysis for the amount of Ki-67 and wild-type p53 expression. All patients had a history of breast cancer and a family history of breast or ovarian cancer. RESULTS: In the fimbriae, a median of 0.42 % Ki-67 and 0.04 % p53-positive epithelial cells was present, compared to a median of 0.36 % for Ki-67 and 0.05 % for p53 in the fallopian tube. Ki-67 expression decreased significantly with age (r = -0.45, p = 0.028). In contrast, p53 expression was not age-dependent for the whole group of patients (r = 0.25, p = 0.25). Subgroup analysis revealed a difference for p53 expression of the BRCA1 mutation carriers with respect to age (median 0.039 vs. 0.082 % for age less or greater than 50.5 years). Consequently, the p53/Ki-67 ratio showed an age-dependent increase, which was accelerated in the BRCA1-positive patients. CONCLUSIONS: Ki-67 and p53 expression varies in morphologically normal tubal epithelial cells depending on age and BRCA1 mutation status. This may reflect an altered and age-dependent DNA repair in BRCA1 mutation carriers and may be related to increased risk of ovarian cancer arising in the fallopian tube.