Ovarian steroids modulate the systemic inflammatory response OF COWS challenged with lipopolysaccharide (LPS) intrauterine infusion.

Postpartum uterine infections of dairy cows promote a local and systemic inflammation and interfere with reproductive efficiency. The aim of this study was to evaluate the effect of steroid hormones including progesterone (P4) and estradiol (E2) on the systemic inflammatory response of cows after being challenged with an intrauterine infusion of lipopolysaccharide (LPS). For this, a hemogram and serum dosage of haptoglobin (Hp) in eight primiparous Gir cows ovariectomized were performed on day (day 0) and after 24 h (day +1). Four cows (n = 4) were challenged (day 0) with 20 mL of 0.9% NaCl + 12.5 µg/kg LPS, and four cows (n = 4) were challenged (day 0) with 20 mL of 0.9% NaCl. For this, the study was divided in four experimental groups as: (1) Control group: without any hormonal treatment before day 0; (2) Group 24 h - E2: 1 mg of estradiol benzoate 24 h before (day -1); (3) Group 24 h - P4: 2.0 g of P4 device 24 h before (day -1); (4) Group 14 d - P4: 2.0 g of P4 device 14 days before (day -14). In the systemic response to LPS, there was an increase in Hp (control group; 24 h - P4 group; 14 d - P4 group), and on day +1 the Hp of 14 d - P4 group was higher when compared to the other groups. On day 0, the 14 d - P4 group had an increase in circulating leukocytes and lymphocytes cells than the control group (P < 0.01). On day +1 after LPS-challenge the 14 d - P4 group showed a decrease in circulating lymphocytes, eosinophils, and monocytes (P < 0.05). A neutrophilia with left shift in the two treatments with P4 (day +1), in addition to a thrombocytopenia and lower platelets compared to the 24 h - E2 group (P < 0.05) (day 0) were recorded. It was concluded that ovariectomized cows challenged with LPS, previously submitted to steroid hormones induce a systemic inflammatory response. Also, the systemic response is more intense after previous prolonged exposure to P4 and less intense after exposure to E2. This study provided important information relating the effect of ovarian steroids on the systemic inflammatory response of cows challenged with intrauterine LPS.

Medicinal electrochemistry: integration of electrochemistry, medicinal chemistry and computational chemistry.

Over the last centuries, there were many important discoveries in medicine that were crucial for gaining a better understanding of several physiological processes. Molecular modelling techniques are powerful tools that have been successfully used to analyse and interface medicinal chemistry studies with electrochemical experimental results. This special combination can help to comprehend medicinal chemistry problems, such as predicting biological activity and understanding drug action mechanisms. Electrochemistry has provided better comprehension of biological reactions and, as a result of many technological improvements, the combination of electrochemical techniques and biosensors has become an appealing choice for pharmaceutical and biomedical analyses. Therefore, this review will briefly outline the present scope and future advances related to the integration of electrochemical and medicinal chemistry approaches based on various applications from recent studies.

Cutaneous loxoscelism caused by Loxosceles similis venom and neutralization capacity of its specific antivenom.

Members of the spider genus Loxosceles pose a marked health risk to humans because of the seriousness of the necrotic and systemic effects of their bite, known as loxoscelism. The recent confirmation of Loxosceles similis in residences of Belo Horizonte in Minas Gerais Province, Brazil increases the local potential risk of loxoscelism at higher levels. The first characterization of the venom from this species showed that its main biological effects had a similar intensity as other species (e.g. Loxosceles intermedia, Loxosceles laeta, and Loxosceles gaucho). Therefore, we wished to further analyse the biological activity of the L. similis venom as well as the capacity of anti-L. similis-venom serum to reduce dermonecrotic effects to rabbit skin. Histological analysis of rabbit skin 2, 4 and 8h after intradermal injection of L. similis venom demonstrated a dense inflammatory infiltrate, edema, degeneration and necrosis of the skin muscle, dissociation of collagen fibers, and disruption of reticular fibers. Importantly, pre-incubation of the venom with anti-L. similis-venom serum significantly decreased all of these effects. Anti-L. similis antivenom generated antibodies that were strongly reactive to L. similis venom and capable of neutralizing the dermonecrotic effects in rabbits caused by this venom. Moreover, the antivenom significantly reduced the sphingomyelinase activity of L. similis crude venom. Venoms produced by male and female spiders were equally reactive towards anti-L. similis and anti-L. intermedia antivenoms, but female venom induced larger lesions on rabbits. In contrast, female venom acted as an immunization enhancer and protected animals from L. similis envenomation to a greater degree than male venom. In conclusion, the results shown in this study for L. similis antivenom merits a more in depth study of its properties, which may become a valuable tool against loxoscelism.

Atypical femoral fractures during prolonged use of bisphosphonates: short-term responses to strontium ranelate and teriparatide.

CONTEXT: Atypical femoral fractures have rarely been reported in women taking bisphosphonates, but this is still a controversial issue. Data are derived mainly from observation studies because a post hoc analysis from a randomized clinical trial did not find any such association. OBJECTIVE: The aim of this study was to report three cases of what are considered atypical femoral fractures and their responses to the use of strontium ranelate and teriparatide. PATIENTS: We studied three postmenopausal women with a diagnosis of osteoporosis who suffered fractures of the subtrochanteric region and femoral diaphysis with no major trauma while on long-term use of bisphosphonates. RESULTS: All the major features of atypical femoral fractures highlighted in the Task Force Report of the American Society for Bone and Mineral Research were present in the three cases. They had had unconsolidated fractures for approximately 1 yr before being referred to our center. After 3 months on strontium ranelate 2 g/d, serum osteocalcin and serum ß-carboxyterminal telopeptide had increased in case 1 by 125 and 100%, respectively, and in case 2 by 50 and 22%, respectively, with total closure of the fracture. In case 3, after 1 month on teriparatide 20 µg/d, a radiographic closure of the fracture was achieved, and 3 months later serum osteocalcin and serum ß-carboxyterminal telopeptide had increased by 300 and 22%, respectively. CONCLUSION: Our finding showed that both teriparatide and strontium ranelate had a rapid bone anabolic effect on unhealed atypical fractures associated with chronic bisphosphonate use.

Fine-needle aspiration cytopathology of malignant fibrous histiocytoma.

BACKGROUND: Most pathologists generally accept malignant fibrous histiocytoma (MFH) as the most common soft tissue sarcoma in adults. This study examines the authors' aspiration cytopathology experience with this tumor, describes its cytomorphology, and determines the reliability of such a diagnosis by fine-needle aspiration biopsy (FNAB). METHODS: The authors' files were reviewed for cases diagnosed as MFH by FNAB, and for surgical pathology cases of MFH previously aspirated but not diagnosed as such by cytology. RESULTS: Fifty-two cases of MFH (by FNAB or histology) were recovered from the combined files; 42 aspirates had tissue confirmation. Patient age ranged from 15-88 years (mean, 63 years); the male:female ratio was 1.2. Thirty aspirates were from primary tumors, and 12 were from recurrences or metastases. From the 29 aspirates diagnosed as MFH, 24 (83%) were determined to be MFH on subsequent surgical excision. Four of the remaining cases were other sarcoma subtypes, and there was one organizing thrombus (false-positive). The remaining 13 aspirates were identified as unqualified sarcoma (11 cases) or a different sarcoma subtype (2 cases). Eleven of these were histologically diagnosed as MFH, and 2 as other sarcomas. No single cytologic feature or combination of features distinguished MFH. Patterns ranged from single cells to large storiform fragments. Spindled, plasmacytoid, and pleomorphic cell shapes were found; pleomorphic cells were often multinucleated. All cases of MFH had malignant nuclear morphology. Diagnostic pitfalls included low cellularity, obscuring blood and inflammation, and inadequate clinical and/or radiologic information. CONCLUSIONS: The diagnostic role of FNAB in soft tissue lesions remains controversial. FNAB is important in the initial triage of patients with soft tissue tumors, and is particularly accurate for confirming recurrent or metastatic disease. Although making an initial diagnosis of sarcoma by FNAB is reliable, specific subtyping of them as MFH is more problematic.

Analysis of p53 expression in osteosarcoma of the jaw: correlation with clinicopathologic and DNA ploidy findings.

The objective of this study was to determine whether p53 expression correlated with clinicopathological and DNA ploidy in osteosarcoma of the jaw, a particular subtype of osteosarcoma associated with an older age at presentation, longer median survival, rare metastasis, and death due to uncontrolled local recurrence. Seventeen cases of osteosarcoma of the jaw were stained for p53 using CM1 antibody (Novocastra). Eight cases (47.5%) showed nuclear staining in more than 10% of the neoplastic nuclei. Ploidy analysis showed 13 aneuploid (eight p53+) and three diploid (none p53+) tumors. No significant relationship was found between p53 positivity and clinicomorphological features, DNA ploidy or survival. p53-positive cases were, however, more commonly associated with aneuploidy and chondroblastic differentiation. These results indicate that p53 immunostaining does not seem to provide prognostic information in osteosarcoma of the jaw.

Alveolar adenoma of the lung: further characterization of this uncommon tumour.

Alveolar adenoma of the lung is a poorly characterized, uncommon pulmonary lesion with proliferation of alveolar epithelium and septal mesenchyme. We describe the electron microscopy, immunohistochemistry and DNA flow cytometry in a case of alveolar adenoma in a 55-year-old woman. Alveolar adenoma appears to be a distinct benign neoplasm of the alveolar structures. Our findings further suggest that it is not a precursor of bronchioloalveolar carcinoma or other type II pneumocyte lesions of presumed malignant potential.

Mitochondria-rough endoplasmic reticulum complexes in a malignant fibrous histiocytoma.

Mitochondria-rough endoplasmic reticulum complexes identical to the ones usually found in chordoma were frequently observed in tumors cells of a malignant fibrous histiocytoma arising in the left thigh of a 48-year-old woman. Although the significance of these structures is unknown, this finding is consistent with the known transformation of chordoma into malignant fibrous histiocytoma.

Fine-needle aspiration cytology of myositis ossificans: a case report.

This report describes the cytological findings of a case of myositis ossificans in a 16-yr-old girl. Clinically and radiologically she was suspected to have a malignant soft tissue tumor. This was not confirmed by fine-needle aspiration cytology and a diagnosis of benign lesion, probably myositis, was given. This diagnosis was confirmed by histological examination.