Evaluation of the analgesic effects of diclofenac as a premedication drug in dogs undergoing ovariohysterectomy.

Pre-emptive analgesia consists of administering drugs such as opioids and nonsteroid anti-inflammatory drugs. This study aims to evaluate the intraoperative antinociceptive effects of diclofenac administered alone in premedication or combined with morphine along with its potential influence on recovery of dogs undergoing ovariohysterectomy. A total of 34 dogs (ASA I or II) admitted for ovariohysterectomy were randomly allocated into three groups according to the drugs given in premedication: Diclofenac (D) (n = 11), Morphine (M) (n = 13) and Diclofenac-Morphine (DM) (n = 10) groups. Induction and maintenance of anesthesia were standardized in all dogs. To assess intraoperative nociception, the heart rate (HR) and mean arterial pressure (MAP) were recorded during the surgery and at predefined time points: St (steady-state), Cut (cutaneous incision), P1 (first ovarian manipulation), P2 (second ovarian manipulation) and Cerv (cervical manipulation). The dynamic variation of HR (ΔHR) and MAP (ΔMAP) over 2 min was calculated at each time point. After extubation, early quality of recovery was assessed. Compared to St, a significant increase in HR and MAP at P1, P2 and Cerv was shown in all groups. MAP in the M group was lower at St than in the other groups. The dynamic variation of HR (ΔHR) and MAP (ΔMAP) was significantly less important at P2 and Cerv compared to P1 only in the DM group. Also, a better quality of recovery was shown in the D group compared to the M and DM groups. Diclofenac may be considered a suitable premedication drug and a part of a multimodal anesthetic approach in dogs.

Early inherited risk for anxiety moderates the association between fathers' child-centered parenting and early social inhibition.

Studies of the role of the early environment in shaping children's risk for anxiety problems have produced mixed results. It is possible that inconsistencies in previous findings result from a lack of consideration of a putative role for inherited influences moderators on the impact of early experiences. Early inherited influences not only contribute to vulnerabilities for anxiety problems throughout the lifespan, but can also modulate the ways that the early environment impacts child outcomes. In the current study, we tested the effects of child-centered parenting behaviors on putative anxiety risk in young children who differed in levels of inherited vulnerability. We tested this using a parent-offspring adoption design and a sample in which risk for anxiety problems and parenting behaviors were assessed in both mothers and fathers. Inherited influences on anxiety problems were assessed as anxiety symptoms in biological parents. Child-centered parenting was observed in adoptive mothers and fathers when children were 9 months old. Social inhibition, an early temperament marker of anxiety risk, was observed at child ages 9 and 18 months. Inherited influences on anxiety problems moderated the link between paternal child-centered parenting during infancy and social inhibition in toddlerhood. For children whose birth parents reported high levels of anxiety symptoms, greater child-centered parenting in adoptive fathers was related to greater social inhibition 9 months later. For children whose birth parents reported low levels of anxiety symptoms, greater child-centered parenting in adoptive fathers was related to less social inhibition across the same period.

Synthesis and characterization of a diruthenium-ibuprofenato complex comparing its anti-inflammatory activity with that of a copper(II)-ibuprofenato complex.

The ibuprofen complex of diruthenium(II,III) was prepared and characterized by electronic (UV-Vis) and vibrational (FTIR) spectroscopies and thermogravimetry. The copper(II)-ibuprofenato complex was prepared by a different route from that described in the literature. Both complexes were tested in vivo for anti-inflammatory activity. Oral administration of the two complexes inhibited development of carrageenin-induced edema in rats, this inhibition being similar to that observed for oral administration of the parent drug (free ibuprofen). However, gastric irritation was lower as compared to that of ibuprofen. Diruthenium-ibuprofenato exhibited a protective effect at light intensity ulceration while the copper-ibuprofenato complex was more effective in the protection of severe intensity ulceration.

A circular dichroism and fluorescence quenching study of the interactions between rhodium(II) complexes and human serum albumin.

Various divalent rhodium complexes Rh2(L)4 (L = acetate, propionate, butyrate, trifluoroacetate and trifluoroacetamidate) have been found to bind to non-defatted human serum albumin (HSA) at molar ratios about 8:1. The circular dichroism measurements showed that the more liposoluble carboxylates, butyrate and trifluoroacetate, caused the major alterations of the secondary structure of HSA. Stern-Volmer constants for the fluorescence quenching of the buried Trp214 residue by these complexes were also higher for the lipophilic metal compounds. In the case of the rhodium carboxylates it was observed that their denaturating and quenching properties could be explained in terms of their liposolubilities: the higher their lipophilic characters, the higher their abilities to penetrate inside the protein framework leading to structural alterations, and the closer they could get to the Trp residue causing fluorescence quenching. The liposoluble amidate complex, Rh2 (tfc)4, presented an intermediate quenching and did not cause structural alterations in the protein, presumably not penetrating inside the peptidic backbone. This study shows that it is possible to design new antitumor metal complexes which bind, to a large extent, to a transport protein causing little structural damage.

Encapsulation and release of rhodium(II) citrate and its association complex with hydroxypropyl-beta-cyclodextrin from biodegradable polymer microspheres.

Rhodium(II) carboxylates and their derivatives constitute a promising class of second-generation transition metal compounds with anticancer properties. While most transition metal anticancer compounds chelate DNA and cause extensive chromosomal damage, rhodium(II) carboxylates act on the enzyme DNA polymerase alpha and hence cause minimal chromosomal damage. Rhodium(II) citrate, a recent member of the rhodium(II) carboxylate family is highly promising as an antitumor agent. However, due to its high water solubility, a high systemic dose is necessary to achieve efficacy. In this paper, we have explored the complexation of rhodium(II) citrate with hydroxypropyl-beta-cyclodextrin as a means to improve encapsulation and release kinetics from poly(dl-lactic-co-glycolic) acid (PLGA) and poly(anhydride) microspheres. We observed that complexation of rhodium(II) citrate with hydroxypropyl-beta-cyclodextrin significantly increased both the encapsulation efficiency and duration of release in both polymer systems.

Survival and Histopathological Study of Animals Bearing Ehrlich Tumor Treated With a Rhodium(II) Amidate.

The survival of 90% of a tumor-bearing population treated with the complex Rh(2) (CF(3)CONH)(4) was examined and the pharmacological parameter Surv(90) determined. Histopathological alterations raised for this drug in several tissues were studied in Balb-c mice. A Surv(90) dose of 3.8x 10(-5) mol/kg was found.

Water Soluble Cyclophosphamide Adducts of Rhodium(II) Keto-Gluconate and Glucuronate. Synthesis, Characterization and In Vitro Cytostatic Assays.

The synthesis, characterization and biological assays of two new rhodium carboxylate sugar derivatives and respective cyclosphosphamide adducts are described. The compounds, characterized by (13)C and (1)H NMR, infrared and UV-visible spectra, presented high water solubility and hydration grades were confirmed given the concordance between thermal and CHN analyses. The adducts were active in vitro against K-562 cells.

Distribution of rhodium in mice submitted to treatment with the adduct of rhodium propionate and sodium isonicotinate.

The distribution of rhodium in Balb/c mice following intraperitoneal (ip) administration of a solution of adduct of rhodium propionate and sodium isonicotinate has been investigated. The metal concentration was determined in blood and in the following organ tissues: brain, heart, lung, liver, spleen, kidney, testes, and uterus/ovary, and the rhodium concentration was obtained by Inductively Coupled Argon Atomic Emission Spectroscopy (ICP-AES). The metal was detected in all organ tissues examined, mainly in spleen, liver, uterus/ovary and heart. Nine days after the injection, traces of rhodium were found in the liver and kidneys and, twenty days after the injection, only in the liver.

Rh(2)(CF(3)CONH)(4): The First Biological Assays of a Rhodium (II) Amidate.

The rhodium (II) complexes Rh(2)(tfa)(4).2(tfac) and Rh(2)(tfacam)(4) (tfacam = CF(3)CONH-,tfa = CF(3)COO-,tfac = CF(3)CONH(2)) were synthesized and characterized by microanalysis and electronic and vibrational spectroscopies. Rh(2)(tfacam)(4) was tested both in vitro (U937 and K562 human leukemia cells and Ehrlich ascitic tumor cells) and in vivo for cytostatic activity and lethal dose determination, respectively. This is the first rhodium tetra-amidate to have its biological activity evaluated. The LD(50) value for Rh(2)(tfacam)(4) is of the same order as that of cisplatin, and it was verified that the rhodium complex usually needs lower doses than cisplatin to promote the same inhibitory effects.

Laparoscopic patching of crack cocaine-induced perforated ulcers.

Since the advent of "crack" cocaine use in the United States as an illicit drug, crack-related perforated ulcers have been reported in the surgical literature. An ischemic process has been postulated as a cause of these perforations. As such, an acid-reducing operative procedure is not recommended. Omental patching of these ulcers has been recommended as the procedure of choice. With the advent of laparoscopic techniques in general surgery, it is now possible to perform this procedure laparoscopically. Laparoscopy may afford the advantages of reduced morbidity, decreased hospital stay, and results potentially equal to the open technique. We present three patients with crack-related perforated ulcers that have been repaired with laparoscopic-assisted patching techniques.

Water-soluble rhodium(II) carboxylate adducts: cytotoxicity of the new compounds.

Rhodium(II) carboxylate (acetate, propionate, and butyrate) adducts with isonicotinic acid (Hisonic) were prepared for study. Elemental analyses and electronic spectroscopy show that the adducts contain two isonicotinic acid ligands coordinated in the axial position at the pyridinic nitrogen. The in vitro (K562 human leukemic cell line) assay and LD10 in mice results, in addition to tests of solubility, suggest that, in the presence of blood lipids or cellular membrane, the adducts dissociate into the parent compounds and the rhodium(II) carboxylate enters the cell to carry out its biological effects.

1,000 consecutive ultrasounds for blunt abdominal trauma.

Diagnostic peritoneal lavage (DPL) and computed tomography (CT) are the primary diagnostic modalities used in the evaluation of patients with suspected blunt abdominal trauma (BAT). DPL is fast and accurate but is associated with complications. CT is also accurate, yet requires stability and transportability of the patients. Ultrasound (US) has been suggested as an aid in evaluating BAT. We evaluated US in the initial assessment of BAT in 1000 patients. Patients were eligible for the study if they met specified trauma criteria and had suspected BAT. We then followed the outcome of the patients and their further work-up. US showed a sensitivity of 88%, a specificity of 99%, and an accuracy of 97% for detecting intraabdominal injuries. We conclude that emergency ultrasound may be used as the initial diagnostic modality for suspected blunt abdominal trauma.

Antitumor effects of rhodium (II) complexes on mice bearing Ehrlich tumors.

Rhodium (II) trifluoroacetate (TFARh), rhodium (II) trifluoroacetate adduct with sulfadiazine (TFARh.Sd) and rhodium (II) acetate adduct with sulfisoxazole (RhSx) were tested in mice for acute toxicity, antitumoral activity against Ehrlich ascites carcinoma and for viability of Ehrlich tumor cells in culture. At ip doses up to 60 mumol/kg (40-70 and 59 mg/kg, respectively), these compounds had no toxic effects up to 14 days. At ip doses of 10 mumol kg-1 day-1 for 5 days, TFARh and TFARh.Sd significantly increased the survival rate of mice bearing Ehrlich ascites cells (probability of survival to the end of 34th day, controls = 0.23, TFARh = 0.85, TFARh.Sd = 0.74). No significant effect was observed for RhSx. In vitro, these rhodium complexes at 40 microM significantly increased the number of dead cells in cultured Ehrlich tumor cells.

Antitumor effects of rhodium (II) complexes on mice bearing Ehrlich tumors

Rhodium (II) trifluoracetate (TFARh), rhodium (II) trifluoracetate adduct with sulfadiazine (TFARh.Sd) and rhodium (II) acetate adduct with sulfisoxazole (RhSx) were tested in mice for acute toxicity, antitumoral activity against Ehrlich ascites carcinoma and for viability of Ehrlich tumor cells in culture. At ip doses up to 60 µmg/kg (40-70 and 59 mg/kg, respectively), these coumpounds had no toxic effects up to 14 days. At ip doses of 10 µmol Kg-1 day-1 for 5 days, TFARh and TFARh.Sd significantly increased the survival rate of mice bearing Ehrlich ascites cells (probability of survival to the end of 34th day, controls = 0.23, TFARh = 0.85, TFARh.Sd = 0.74). No significant effect was observed for RhSx. In vitro, these rhodium complexes at 40 µM significantly increased the number of dead cells in cultured Ehrlich tumor cells

Adducts of nitroimidazole derivatives with rhodium(II) carboxylates: syntheses, characterization, and evaluation of antichagasic activities.

Adducts of several rhodium(II) carboxylates with two antiparasitic nitroimidazole ligands were prepared and characterized by elemental microanalysis, thermogravimetry, spectrophotometry (IR, UV, and visible), and proton magnetic resonance. Results of elemental and thermogravimetric analyses were consistent with the general formula Rh2(RCOO)4. 2L (R = aliphatic or aromatic carboxylic groups; L = metronidazole or benznidazole). The reddish-brown color of the adducts as well as their visible spectra suggest axial coordination of the nitroimidazole ligands through nitrogen atoms. NMR spectra indicate N3 as the coordinating atoms. Screening tests performed on cultures of T. cruzi indicate that aliphatic complexes--particularly propionate and acetate adducts--were more active than their aromatic counterparts, the same being observed with benznidazole adducts in relation to their metronidazole analogues. Evaluated for their usefulness as transfusion prophylactic agents against Chagas' disease, propionate derivatives failed to sterilize T. cruzi infected blood. An oral toxicity assay in mice showed mild toxic effects with daily doses of 5 mg/kg for 20 days.

Synthesis, characterization, and biological screening of a copper flurbiprofen complex with anti-inflammatory effects.

The flurbiprofen complex of copper(II) was prepared and characterized by IR, UV-VIS and EPR Spectroscopy, magnetic susceptibility, and thermogravimetric analysis. The compound was tested for in vivo anti-inflammatory and analgesic activities in rats. The inhibitory effect on carrageenin-induced paws inflammation and analgesic effect of copper flurbiprofen complex were similar to those of free flurbiprofen. However, the copper complex produced less gastric irritation than the parent drug.

Antitumor effects of rhodium (II) citrate in mice bearing Ehrlich tumors.

Rhodium II citrate was tested in mice for acute toxicity, antitumoral activity against Ehrlich ascites carcinoma and inhibition of DNA synthesis by Ehrlich tumor, malignant adrenocortical cells (Y-1) and normal adrenocortical cells (AR-1). At ip doses up to 260 mg/kg, the compound had no toxic effects for up to 14 days. The same total dose given over 4 days significantly increased the survival rate of mice bearing Ehrlich ascites cells. Thymidine incorporation by Ehrlich tumor, Y-1 and AR-1 cells in vitro was inhibited 50% by 0.1 to 0.2 mM concentrations of the compound. We conclude that the increased survival of the tumor-bearing mice was due at least in part to the inhibition of DNA synthesis with a consequent reduction of cell division and tumor growth.

Antitumor effects of Rhodium (II) citrate in mice bearing Chrlich tumors

Rhodium II citrate was tested in mice for acute toxicity, antitumoral activity against Ehrlich ascites carcinoma and inhibition of DNA synthesis by Ehrlich tumor, malignant adrenocortical cells (Y-1) and normal adrenocortical cells (AR-1)_. At ip doses up to 260 mg/Kg, the compound had no toxic effects for up to 14 days. The same total dose given over 4 days significantly increased the survial rat of mice bearing Ehrlich ascites cells. Thymidine incorporation by Ehrlkich tumor, Y-1 cells in vitro was inhibited 50% by a.1 to 0.2 mM concentrations of the compound. We conclude that the increase survival of the tumor-bearing mice was due at least in part to the inhibition of DNA synthesis with a consequet reduction of cell division and tumor growth