growing political momentum to definitively address tuberculosis, could all make ending the pandemic within a generation more feasible than ever before. Moving forward with bold, comprehensive strategies Globally, the priority must be to deliver person-centred and family-centred services to all individuals with tuberculosis who present to care. This approach means ensuring that high-quality diagnostics, treatment, and prevention modalities are available to all, wherever they seek care. Improving quality of tuberculosis care in the private sector is crucial to end tuberculosis in high incidence countries such as India, the country with the highest tuberculosis burden. Modelling shows that optimising private sector engagement in India could avert 8 million deaths from tuberculosis between 2019 and 2045 (appendix p 3). In high drug-resistant tuberculosis burden countries, access to rapid drug susceptibility testing (DST) and second-line drugs is essential to success. In Moldova, where more than 25% of all tuberculosis cases are drug-resistant, improving access to DST and second-line drugs would reduce mortality from drug-resistant tuberculosis by 44% in the coming generation (appendix p 3). Secondly, tuberculosis programme budgets must increase to enable reaching these people and populations at high risk of tuberculosis. In Kenya, for example, where the proportions of HIV and tuberculosis coinfection are high, scaling up access to both antiretroviral therapy and tuberculosis preventive therapy can help save an additional 3 million lives over the next generation (appendix p 3). However, ultimately, the fight against tuberculosis will not be won unless countries also ensure that everyone, not just high-risk groups, can access essential health Key messages The Commission recommends five priority investments to achieve a tuberculosis-free world within a generation. These investments are designed to fulfil the mandate of the UN High Level Meeting on tuberculosis. In addition, they answer the question of how countries with high-burden tuberculosis and their development partners should target their future investments to ensure that ending tuberculosis is achievable. Invest first to ensure that high quality rapid diagnostics and treatment are provided to all individuals receiving care for tuberculosis, wherever they seek care This priority includes rapid drug susceptibility testing and second-line treatment for resistant forms of tuberculosis. Achieving universal, high-quality person-centred and family-centred care-including sustained improvement in the performance of private sector providers-usually should be the top policy and budget priority. Reach people and populations at high risk for tuberculosis (such as household and other close contacts of people with tuberculosis, and people with HIV) and bring them into care Active case-finding and treatment in high-risk populations demands adequate resources to reach and care for these populations. At the same time, reaching certain high-risk populations, such as people co-infec...

The pharmacokinetics of YM-13115, ceftriaxone, and ceftazidime were studied in rats, dogs, and rhesus monkeys (only YM-13115 and ceftriaxone were studied in rhesus monkeys). The plasma half-lives in rats were 48 min for YM-13115, 34 min for ceftriaxone, and 14 min for ceftazidime. In dogs, they were 21.9 min for YM-13115, 50.7 min for ceftriaxone, and 49.0 min for ceftazidime. In monkeys, they were 5.30 h for YM-13115 and 3.40 h for ceftriaxone. The 24-h urinary recoveries in rats were 26.7% of the dose for YM-13115, 32.0% for ceftriaxone, and 97.1% for ceftazidime. In dogs, they were 13.3% for YM-13115, 62.5% for ceftriaxone, and 86.3% for ceftazidime. In monkeys, they were 22.5% for YM-13115 and 29.3% for ceftriaxone. The 24-h biliary recoveries in rats were 72.2% for YM-13115, 61.8% for ceftriaxone, and 0.63% for ceftazidime. Fig. 1) is a new parenteral cephalosporin developed at Central Research Laboratories, Yamanouchi Pharmaceutical Co., Ltd., Tokyo, Japan. As will be detailed elsewhere, this compound is highly active in vitro against gram-negative bacteria, including Pseudomonas aeruginosa. In the present report, the pharmacokinetics of YM-13115, ceftriaxone, and ceftazidime in rats, dogs, and rhesus monkeys are compared.Antibiotics. YM-13115 and the reference compounds, ceftazidime and ceftriaxone, were synthesized at Central Research Laboratories, Yamanouchi Pharmaceutical Co., Ltd., Tokyo, Japan.Experimental animals. Included in this study were male Sprague-Dawley rats (body weight, 200 to 250 g), three female beagle dogs (body weight, 12.2 to 12.6 kg), and two male rhesus monkeys (body weight, 5.3 and 5.9 kg).Administration of antibiotics. Each of the above antibiotics, dissolved in sterile physiological saline just before use, was administered intravenously (bolus injection) at a dose of 20 mg/kg to rats, dogs, and monkeys. The three dogs received YM-13115, ceftriaxone, and ceftazidime at 1-week intervals in a parallel fashion. The two monkeys received YM-13115 and ceftriaxone at the same interval.Plasma samples. Rats in groups of three were sacrificed with ether 5, 15, 30, 60, 90, and 120 min after drug administration. Blood was drawn from the inferior vena cava and heparinized. In the tests with dogs and monkeys, blood samples were taken from each dog at 5, 10, 20, 30, and 45 min and 1, 1.5, 2, 4, and 6 h after drug administration and from each monkey at 5, 15, 30, and 45 min and 1, 1.5, 2, 3, 4, and 6 h after administration and heparinized. Plasma was separated from these heparinized blood samples by centrifugation at 1,400 x g at 4°C, removed by aspiration, and stored at -20°C until assayed, usually within 3 days.Urine and bile specimens. Urine specimens were collected 0 to 3, 3 to 6, and 6 to 24 h (rats and dogs) or 0 to 6 and 6 to 24 h (monkeys) after intravenous injection of each antibiotic. * Corresponding author. 204Rats, dogs, and monkeys were maintained in metabolism cages for collection of urine, except that dogs underwent bladder catheterization for each terminal specimen.Biliary excreti...

The pharmacokinetics of cefpiramide (SM-1652)

To characterize a new function of the watersoluble vitamin, biotin, in reproduction and early growth in mammals, the effects of high dietary doses of biotin on early spermatogenesis were biochemically and histologically investigated in male rats. Weaned rats were fed a CE-2 (control) diet containing 0.00004% biotin, or a control diet supplemented with 0.01%, 0.1%, or 1.0% biotin. Pair-fed rats were fed a control diet that was equal in calories to the amount ingested by the 1.0% biotin group, because food intake was decreased in the 1.0% biotin group. Food intake and body weight gain were lower in the 1.0% biotin group than in the control group. The kidney, brain and testis weights were significantly lower in the 1.0% biotin group than in the pair-fed group after 6 weeks of feeding. The accumulation of biotin in the liver and testis increased in a dose-dependent manner. In the 1.0% biotin group, the number of mature sperm was markedly lower, that of sperm with morphologically abnormal heads, mainly consisting of round heads, had increased. In addition, the development of seminiferous tubules was inhibited, and few spermatogonia and no spermatocytes were histologically observed. These results demonstrated that the long-term intake of high-dose biotin inhibited spermatogenesis in young male rats.

We suggest that the number of people with HIV among Japanese has continued to increase, and that the increase in the number of AIDS cases among Japanese is now slowing.