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Opioids are essential for use in rhesus macaques (Macaca mulatta) that require multimodal analgesia or those unable to receive NSAID as part of their pain management plan. The current opioid epidemic has universally limited the availability of these vital analgesics, compelling clinicians to investigate other options including novel opioid formulations. A commercially available injectable, long-lasting, highly concentrated buprenorphine solution (HCBS) provides therapeutic plasma concentrations lasting 24 h after a single dose in cats ( Felis catus). We hypothesized that this same HCBS would achieve therapeutic concentrations (≥0.1 ng/mL) for at least 24 h in rhesus macaques. In the current study, 6 healthy, adult rhesus macaques were included in a randomized, 2-period, 2-treatment crossover study. The low dose (0.24 mg/kg SC) achieved a peak plasma concentration of 19.1 ± 5.68 ng/mL at 0.308 ± 0.077 h, with an AUC of 236.4 ± 22.5 h/ng/mL and terminal elimination half-life of 19.6 ± 4.02 h; for the high dose (0.72 mg/kg SC), these parameters were 65.2 ± 14.7 ng/mL, 0.034 ± 0.004 h, 641.3 ± 79.4 h/ng/mL, and 20.6 ± 2.30 h, respectively. The mean plasma concentrations for the low and high doses in rhesus macaques significantly exceeded the therapeutic threshold for 48 and 72 h, respectively. One macaque showed mild somnolence at both doses, and another showed mild pruritus at both doses. These findings show that subcutaneous administration of HCBS provides prolonged and long-lasting therapeutic plasma levels for 48 to 72 h dosing without problematic adverse effects and thus represents a potential new analgesic alternative.

Opioids are essential for use in rhesus macaques (Macaca mulatta) that require multimodal analgesia or those unable to receive NSAID as part of their pain management plan. The current opioid epidemic has universally limited the availability of these vital analgesics, compelling clinicians to investigate other options including novel opioid formulations. A commercially available injectable, long-lasting, highly concentrated buprenorphine solution (HCBS) provides therapeutic plasma concentrations lasting 24 h after a single dose in cats (Felis catus). We hypothesized that this same HCBS would achieve therapeutic concentrations (≥ 0.1 ng/mL) for at least 24 h in rhesus macaques. In the current study, 6 healthy, adult rhesus macaques were included in a randomized, 2-period, 2-treatment crossover study. The low dose (0.24 mg/kg SC) achieved a peak plasma concentration of 19.1 ± 5.68 ng/mL at 0.308 ± 0.077 h, with an AUC of 236.4 ± 22.5 h/ng/mL and terminal elimination half-life of 19.6 ± 4.02 h; for the high dose (0.72 mg/kg SC), these parameters were 65.2 ± 14.7 ng/mL, 0.034 ± 0.004 h, 641.3 ± 79.4 h/ng/mL, and 20.6 ± 2.30 h, respectively. The mean plasma concentrations for the low and high doses in rhesus macaques significantly exceeded the therapeutic threshold for 48 and 72 h, respectively. One macaque showed mild somnolence at both doses, and another showed mild pruritus at both doses. These findings show that subcutaneous administration of HCBS provides prolonged and long-lasting therapeutic plasma levels for 48 to 72 h dosing without problematic adverse effects and thus represents a potential new analgesic alternative.

Recently cancer/testis antigens (CTA) have gained lots of attention as targets of immune therapy. However, the therapeutic efficacy of the CTAs single-antigen vaccines is not satisfying due to tumor heterogenicity. Therefore, many studies have focused on the enhancement of their efficacy by utilizing rich sources of tumor-associated antigens for anti-cancer vaccination. In the present study, the testicular germ cells and sperm cells as well-known sources of cancer/testis antigens were investigated for anti-4T1 breast cancer vaccination in BALB/c mice. The testicular germ cells (TGCs) and sperm cells were isolated from male BALB/c mice. The definite number of cells were homogenized and mixed with Bacillus Calmette–Guerin (BCG) for vaccination of female BALB/c mice. The treatment groups underwent 3 times of immunizations with one-week intervals and one week after the last injection, all groups were injected with 4T1 cancer cells. The TGCs + BCG (259.7 ± 39 mm3) and Sperm + BCG (426 ± 52 mm3) groups exhibited a significant decrease in the tumors' volume in comparison with BCG (641.3 ± 102 mm3) and no-treatment (788.1 ± 117 mm3) groups. Therefore, the TGCs + BCG immunized mice had the smallest tumors in comparison with all groups (P

Aims Chronic heart failure (CHF) is frequently associated with a decreased haemoglobin level, whereas the mechanism remains largely unknown. Methods and results One hundred consecutive CHF patients without anaemia or renal dysfunction based on non-cardiac reasons were enrolled. We explored determinants of anaemia (as iron parameters, erythropoietin, hepcidin and kidney function) including red cell volume (RCV) (by a 51 Cr assay) as well as related markers and plasma volume. The influence of each factor on haemoglobin concentrations was determined in a multiple regression model. Mean haemoglobin concentrations were 11.7 +/- 0.8 mg/dL in anaemic CHF patients and 14.4 +/- 1.2 mg/dL in non-anaemic patients. Corrected reticulocytes were lower in anaemic patients (35.1 +/- 15.7 vs. 50.3 +/- 19.2 G/L, P = 0.001), but the RCV was not reduced (1659.3 +/- 517.6 vs. 1826.4 +/- 641.3 mL, P = 0.194). We found that plasma volumes were significantly higher in anaemic CHF patients (70.0 +/- 2.4 vs. 65.0 +/- 4.0%, P0.001). Plasma volume was the best predictor of haemoglobin concentrations in the regression model applied (B = -0.651, P0.001, R(2) = 0.769). Conclusion Haemodilution appears to be the most potent factor for the development of low haemoglobin levels in patients with CHF. Our data support an additional independent, but minor influence of iron deficiency on haemoglobin concentrations in CHF patients.

The eriococcid species, Eriococcus araucariae (Muskell) is considered as an economic pest of Araucaria excelsa at Montazah garden, in Alexandria Governorate, Egypt. This study was carried out from June, 1998 till May, 1999. The obtained data revealed that the numbers of this insect were relatively low in autumn and winter months, then increased from the beginning of May to a total number/tree 72.0 +/- 1.60; continued its increase to reach 200.3 +/- 36.9/tree from the 2nd half of May and during June, July and August, with the highest number of inspected individuals (641.3 +/- 76.8/tree) in the 1st half of July. Thereafter, population began to decrease again from the beginning of September up to the end of April, decreased numbers 51.3 +/- 2.5/tree in the 1st half of September and (1.3 +/- 0.1/tree) in the 2nd half of October. Similarly, the occurrence of both immature stages and adults was also month-dependant all the year round. Adult males appeared three times in June, January and late March. There was a positive and significant relationship between the total population of E. araucariae and the daily mean temperature, wind speed and day light. This relation was negatively significant with the relative humidity.

To determine the short-term results of the Bicarbon (Sorin Biomedica, Saluggia, Italy) heart valve prosthesis at our institution.Between November 1991 and December 1995, 256 patients (mean age 59.9 +/- 9.8 years) underwent valve replacement with a Bicarbon valve prosthesis. The mean ejection fraction was 60 +/- 14.8% and the mean left ventricular end-diastolic pressure 15.9 +/- 8.7 mmHg. Redo (n = 61) and combined procedures (n = 72) were included in this study; mixed types of prostheses were excluded. The procedures were divided into groups: aortic valve replacement (n = 163), mitral valve replacement (n = 60) and aortic-mitral (double) valve replacement (n = 33). Kaplan-Meier survival analysis was performed and predictors for survival were tested univariately and multivariately.The mean follow up was 30 +/- 25.1 months with a total of 7,696 patient-months (641.3 patient-years) and was 100% complete. The Kaplan-Meier survival rate at 48 months was 87 +/- 2%. The valve-related morbidity expressed as linearized incidence rate (% per patient-year) was: anticoagulation bleeding 2.3 +/- 0.6; thromboembolic event 1.0 +/- 0.4; periprosthetic leak 0.6 +/- 0.3; and endocarditis 0.3 +/- 0.2. Univariate significant factors for worse survival were: higher preoperative New York Heart Association (NYHA) functional class, valve implantation site, presence of associated operation, increasing age, decreasing ejection fraction, longer aortic cross-clamp time, and longer cardiopulmonary bypass time. In multivariate analysis longer aortic cross-clamp time and higher preoperative NYHA classification were significant independent predictors.These good short-term results after Bicarbon valve replacement are encouraging and comparable with those obtained with other bileaflet mechanical heart valves. However, further follow up is mandatory.

Using the electrophoretic method, the changes in the catalytic activities of three CK-MM isoforms in multiple sequential serum samples of 12 patients with acute myocardial infarction (AMI) were monitored for 3 days after the onset of chest pain. In post-AMI period, MM3 reached a peak (518.6 U/L) first, on the average 14.0 hours after AMI, followed by MM2 (19.8 h, 640.5 U/L) and MM1 (28.7 h, 641.3 U/L). According to their faster decay from circulation, MM3 had higher fractional disappearance and appearance rates, followed by MM2 and MM1. The MM3/MM1 activity ratio rose beyond the upper limit, found in health subjects, about 3.5 hours after onset of symptom and peaked on an average 10.6 hours after AMI, even earlier than the peaks of all isoforms, CK and CK-MB. On the other hand, our findings indicated these changes in isoform composition can be of value in estimating the time elapsed since the onset of tissue damage; MM3 is the predominant isoform when the tissue necrosis is of relatively recent origin (5-15 h); MM2 is the dominant subband between 15 and 24 hours after AMI, whereas a predominant MM1 band would indicate a significantly longer time period since the injury occurred (24 hours or more). Thus, these characteristics make CK-MM isoforms an earlier and more sensitive indicator of acute release from necrotic myocardium and an effective mean of predicting the time of the onset of AMI.