Pharmacotherapeutic potential of malvidin to cure imidacloprid induced hepatotoxicity via regulating PI3K/AKT, Nrf-2/Keap-1 and NF-κB pathway.

Imidacloprid (IMI) is one of the top-notch insecticides that adversely affects the body organs including the liver. Malvidin (MAL) is a natural flavonoid which exhibits a wide range of pharmacological properties. This research was designed to evaluate the protective ability of MAL to counteract IMI instigated liver toxicity in rats. Thirty-two rats were divided into four groups including control, IMI (5mg/kg), IMI (5mg/kg) + MAL (10mg/kg) and MAL (10mg/kg) alone treated group. The recommended dosages were administrated through oral gavage for 4 weeks. It was revealed that IMI intoxication disrupted the PI3K/AKT and Nrf-2/Keap-1 pathway. Furthermore, the activities of catalase (CAT), glutathione peroxidase (GPx), superoxide dismutase (SOD), heme-oxygenase-1 (OH-1) and glutathione reductase (GSR) were reduced while upregulating reactive oxygen species (ROS) and malondialdehyde (MDA) levels after IMI treatment. Moreover, IMI poisoning increased the levels of ALT (Alanine aminotransferase), AST (Aspartate transaminase), and ALP (Alkaline phosphatase) while reducing the levels of total proteins and albumin in hepatic tissues of rats. Besides, IMI administration escalated the expressions of Bcl-2-associated protein x (Bax) and cysteine-aspartic acid protease-3 (Caspase-3) while downregulating the expressions of B-cell lymphoma 2 (Bcl-2). Similarly, IMI intoxication, increased the levels of Interleukin-6 (IL-6), Nuclear factor kappa-B (NF-κB), Interleukin-1ß (IL-1ß), tumor necrosis factor-α (TNF-α), and the activity of cyclooxygenase-2 (COX-2). Furthermore, IMI disrupted the normal architecture of hepatic tissues. However, MAL treatment remarkably protected the liver tissues via regulating abovementioned disruptions.

Therapeutic potential of salvigenin to combat atrazine induced liver toxicity in rats via regulating Nrf-2/Keap-1 and NF-κB pathway.

Atrazine (ATR) is the second most extensively used herbicide which adversely affects the body organs including liver. Salvigenin (SGN) is a flavonoid which demonstrates a wide range of biological and pharmacological abilities. This study was planned to assess the protective ability of SGN to avert ATR induced liver damage in rats. Thirty-two rats (Rattus norvegicus) were divided into four groups including control, ATR (5 mg/kg), ATR (5 mg/kg) + SGN (10 mg/kg) and SGN (10 mg/kg) alone supplemented group. ATR exposure reduced the expression of Nrf-2 while instigating an upregulation in Keap-1 expression. Furthermore, the activities of catalase (CAT), glutathione peroxidase (GPx), superoxide dismutase (SOD), heme­oxygenase-1 (HO-1) and glutathione reductase (GSR) contents were decreased while increasing reactive oxygen species (ROS) and malondialdehyde (MDA) levels after ATR treatment. Moreover, ATR poisoning increased the levels of ALT, AST, and ALP while reducing the levels of total proteins, and albumin in hepatic tissues of rats. Besides, ATR administration escalated the expressions of Bax and Caspase-3 while inducing a downregulation in the expressions of Bcl-2. Similarly, ATR intoxication increased the levels of Interleukin-6 (IL-6), Nuclear factor kappa-B (NF-κB), Interleukin-1ß (IL-1ß), tumor necrosis factor-α (TNF-α), and the activity of cyclooxygenase-2 (COX-2). Furthermore, ATR disrupted the normal histology of hepatic tissues. However, SGN treatment remarkably protected the liver tissues via regulating antioxidant, anti, inflammatory, anti-apoptotic as well as histology parameters. Therefore, it is concluded that SGN can be used as therapeutic agent to combat ATR-induced hepatotoxicity.

Anatomical Distribution of Ochronotic Pigment in Alkaptonuric Mice is Associated with Calcified Cartilage Chondrocytes at Osteochondral Interfaces.

Alkaptonuria (AKU) is characterised by increased circulating homogentisic acid and deposition of ochronotic pigment in collagen-rich connective tissues (ochronosis), stiffening the tissue. This process over many years leads to a painful and severe osteoarthropathy, particularly affecting the cartilage of the spine and large weight bearing joints. Evidence in human AKU tissue suggests that pigment binds to collagen. The exposed collagen hypothesis suggests that collagen is initially protected from ochronosis, and that ageing and mechanical loading causes loss of protective molecules, allowing pigment binding. Schmorl's staining has previously demonstrated knee joint ochronosis in AKU mice. This study documents more comprehensively the anatomical distribution of ochronosis in two AKU mouse models (BALB/c Hgd-/-, Hgd tm1a-/-), using Schmorl's staining. Progression of knee joint pigmentation with age in the two AKU mouse models was comparable. Within the knee, hip, shoulder, elbow and wrist joints, pigmentation was associated with chondrons of calcified cartilage. Pigmented chondrons were identified in calcified endplates of intervertebral discs and the calcified knee joint meniscus, suggesting that calcified tissues are more susceptible to pigmentation. There were significantly more pigmented chondrons in lumbar versus tail intervertebral disc endplates (p = 0.002) and clusters of pigmented chondrons were observed at the insertions of ligaments and tendons. These observations suggest that loading/strain may be associated with increased pigmentation but needs further experimental investigation. The calcified cartilage may be the first joint tissue to acquire matrix damage, most likely to collagen, through normal ageing and physiological loading, as it is the first to become susceptible to pigmentation.

Dedifferentiated endometrioid adenocarcinoma with trophoblastic components: Prolonged remission after treatment with bleomycin, etoposide, and cisplatin.

Dedifferentiated endometrial adenocarcinoma (DEAC) with trophoblastic components is a rare neoplasm with an aggressive behavior and a poor prognosis. Only seven cases have been reported in the literature. We present a 61-year-old patient who was diagnosed with Stage IB dedifferentiated endometrioid adenocarcinoma with trophoblastic elements. A post-operative ß-hCG was elevated at 1877 mIU/mL. The patient received 6 cycles of carboplatin and paclitaxel with normalization of ß-hCG; however, three months after completion of chemotherapy, her ß-hCG increased to 39 mIU/mL and a mass overlaying the psoas muscle was noted on imaging. The mass was resected and confirmed to be recurrent disease. Four cycles of bleomycin, etoposide, and cisplatin were administered, and the patient remains without evidence of disease 3 years after completing treatment. Due to the small number of reported cases of DEAC with trophoblastic components, there is limited information regarding the appropriate first-line adjuvant chemotherapy regimen.

The impact of tumor size in breast needle biopsy material on final pathologic size and tumor stage: a detailed analysis of 222 consecutive cases.

Tumor size is a significant prognostic indicator for invasive mammary carcinoma. By current standards, this is routinely reported during pathologic evaluation of the definitive excision, but no recommendations exist for reporting tumor size in needle biopsy material. The purpose of this study is to evaluate the relationship between tumor size on breast needle biopsy specimens and that on subsequent definitive excision specimens and to evaluate the impact of the former, if any, in determining the final pathologic tumor stage. This was achieved by an evaluation of 222 consecutive cases of invasive mammary carcinoma for which both the diagnostic biopsy and definitive excision were available for review. Of 200 cases without a history of neoadjuvant therapy, there were 161 (80.5%) cases in which the tumor size on biopsy was smaller, 15 (7.5%) cases in which the sizes were equal, and 24 (12%) in which the size on biopsy was greater, including 6 (3%) cases with no residual tumor on excision. The average size change (excision size minus biopsy size) increased with increasing tumor stage, with these being significantly lower in pT1a compared with pT1b tumors (-0.14 vs. 0.17 mm; P=0.0002), pT1a/b compared with pT1c tumors (0.12 vs. 0.53 mm; P<0.0001), and pT1 compared with pT2/3 tumors (0.32 vs. 2.2 mm; P<0.001). Of the 24 cases in which tumor size on biopsy was greater than that on excision, there were 15 (7.5% of cohort) in which the tumor size on biopsy was the sole determinant of a higher final pathologic T stage. A larger tumor size on biopsy compared with that on excision was significantly associated with a lower final pathologic T stage (P<0.001) but not with patient age, histologic type, histologic grade, mitotic score, or the presence/absence of ductal carcinoma in situ. Evaluation of the remaining 22 cases also showed that there was a clear association between a history of neoadjuvant therapy and the finding of a larger size on biopsy compared with that on excision (P<0.0001). These findings indicate that tumor size on breast needle biopsy is not infrequently larger than that on excision and can also dictate the final pathologic T stage. Accordingly, it is recommended that the greatest extent of invasive carcinoma is reported in all needle biopsy specimens.

Portopulmonary hypertension secondary to congenital extrahepatic portosystemic shunt with heterotaxy and polysplenia: a cause of sudden death in an infant.

Congenital extrahepatic portosystemic shunt (CEPS) is associated with polysplenia and heterotaxy and can cause portopulmonary hypertension. We report a 12-month-old girl who acutely died likely due to portopulmonary hypertension secondary to CEPS associated with heterotaxy and polysplenia. A retrospective radiographic review following her autopsy identified an anatomical explanation for the acute death in an infant.

Clinical, histopathologic, and radiographic indicators of malignancy in head and neck paragangliomas.

OBJECTIVE: The goal of this study is to review our series of head and neck paragangliomas to identify factors that may help in predicting malignancy. STUDY DESIGN: Case series with chart review. SETTING: Academic medical center. SUBJECTS AND METHODS: Subjects with head and neck paragangliomas at our institution from 1976 to current were reviewed. In addition to statistical comparisons of epidemiologic factors, pathologic and radiographic characteristics were reviewed. RESULTS: Of the 84 subjects, there were seven malignant paragangliomas (8%). Age was found to be significantly different between the benign and malignant subgroups, with an average age of 54 ± 16 and 40 ± 12 years, respectively (P = 0.02). Pain was a presenting complaint in five patients with benign disease (6%), and five of the seven malignant patients (71%) presented with pain, showing a significant association between pain and disease type (P < 0.0001). The odds ratio for a patient with pain having a malignant tumor was 36 (95% CI: 5.5-234). Enlarging neck mass was noted in all cases of malignant disease, but only in 31 percent of cases of benign disease (P < 0.0001). In a secondary analysis of carotid body tumors alone, enlarging neck mass was not found to be significant between benign and malignant disease (P = 0.14). However, pain continued to be significantly different, with 67 percent of malignant lesions demonstrating pain, compared with only 11 percent of benign lesions (P = 0.01). CONCLUSION: This study suggests that pain, a rapidly enlarging neck mass, and younger age are predictive factors of underlying malignancy, which should prompt one to consider an aggressive diagnostic and management approach.

Rapid quantitation of hemoglobin S in sickle cell patients using the Variant II Turbo analyzer.

A rapid ( approximately 90 sec), fully automated method is described for quantifying hemoglobin S (HbS) by high performance liquid chromatography (HPLC) using the Bio-Rad Variant II Turbo analyzer. Although this instrument is designed to quantify only blood hemoglobin A1c (HbA1c), we show that it can also quantify accurately, without modification, HbS levels in sickle cell patients, provided the blood samples meet certain conditions. The samples should contain detectable hemoglobin F (HbF), but should not contain hemoglobin C (HbC). Under these conditions, blood HbS levels obtained by this method correlate well with those obtained by agarose electrophoresis (r(2) = 0.97, n = 81 patients). We also show that quantitation of blood HbF in sickle cell patients is more accurate by this method than by agarose electrophoresis when the HbF level is in the range from 0.2 to 10%.