Full Treatment Period Research Articles

Sludge quality after 10-20years of treatment in reed bed systems.

The effect on the environment of the operation of sludge treatment in reed beds (STRB) system is seen as quite limited compared to traditional sludge treatment systems such as mechanical dewatering, drying and incineration with their accompanying use of chemicals and energy consumption. There are several STRB systems in Denmark receiving sludge from urban wastewater treatment plants. Stabilization and mineralization of the sludge in the STRB systems occur during a period between 10 and 20years, where after the basins are emptied and the sludge residue typically is spread on agricultural land. In the present study, the sludge residue quality after treatment periods of 10-20years from four Danish STRBs is presented. After reduction, dewatering and mineralization of the feed sludge (dry solid content of 0.5-3%) in the STRB systems, the sludge residue achieved up to 26% dry solid, depending on the sludge quality and dimensioning of the STRB system. The concentration of heavy metals and hazardous organic compounds in the sludge residue that are listed in the Danish and EU legislation for farmland application of sludge was below the limit values. The nitrogen and phosphorus concentrations as an average in the sludge residue were 28 and 36g/kg dry solid (DS), respectively. In addition, mineralization on average across the four STRB systems removed up to 27% of the organic solids in the sludge. The investigation showed that the sludge residue qualities of the four STRBs after a full treatment period all complied with the Danish and European Union legal limits for agricultural land disposal.

Phase 1b/2a Open-Label, Multiple-Dose, Dose-Escalation Study To Evaluate The Safety and Tolerability Of Intravenous Infusion Of SNS01-T In Patients With Relapsed Or Refractory Multiple Myeloma, Mantle Cell Lymphoma, Or Diffuse Large B Cell Lymphoma

Eukaryotic translation initiation factor 5A (eIF5A) has been implicated in the regulation of cell proliferation, apoptosis, and inflammation, and is the only known protein to be modified by hypusination. Hypusinated eIF5A, the predominant form of eIF5A in cancer cells, is involved in cell survival and activation of inflammatory pathways. In contrast, accumulation of the unhypusinated form of eIF5A is associated with apoptosis and mutants of eIF5A that cannot be hypusinated (e.g. eIF5AK50R) are pro-apoptotic. SNS01-T was designed to treat B-cell cancers and consists of two active components: a plasmid DNA expressing the pro-apoptotic eIF5AK50R under the control of a B cell-specific promoter, and an siRNA against an untranslated region of native eIF5A mRNA. When these two components are combined with linear polyethyleneimine (PEI), the nucleic acids are condensed into nanoparticles for protection from degradation in the blood and enhanced cellular delivery. The mode of action of SNS01-T is siRNA-mediated inhibition of hypusinated eIF5A and simultaneous over-expression of pro-apoptotic eIF5AK50R to induce cell death. In vitro cell studies and in vivo xenograft studies have demonstrated the efficacy of this approach.The safety and tolerability of intravenous administration of SNS01-T is being investigated in a first-in-human Phase1b/2a study in patients with relapsed or refractory multiple myeloma (MM), mantle cell lymphoma (MCL) or diffuse large B cell lymphoma (DLBCL). Eligible patients are being enrolled sequentially into four cohorts at increasing doses. Each patient receives an intravenous infusion of SNS01-T twice weekly for 6 consecutive weeks. Eligible patients must have been diagnosed with MM according to IMWG criteria, or with MCL or DLBCL with histologic confirmation. Patients also must have measurable disease, have relapsed or refractory disease after two or more prior treatment regimens, have a life expectancy of at least 3 months, and not be eligible to receive any other standard therapy known to extend life expectancy. The primary objective is to evaluate the safety and tolerability of multiple escalating doses of SNS01-T. Secondary objectives include analysis of pharmacokinetics, immunogenicity, pro-inflammatory cytokines, and therapeutic efficacy.The required 3 patients per cohort have completed the dosing schedule in cohorts 1 and 2 from a total of 10 patients enrolled (9 patients with MM and 1 with DLBCL). Of the ten patients enrolled, four completed the full treatment period, two did not complete dosing but were evaluable for safety, and four (three in cohort 1 and one in cohort 2) discontinued treatment after fewer than 8 doses and were not evaluable. There were no drug-related serious adverse events or dose limiting toxicities in either cohort 1 or 2.In cohort 1 (0.0125 mg/kg SNS01-T), two of three evaluable patients did not progress on treatment and were considered stable at week 3 and week 6, the end of the dosing regimen. The third patient progressed after receiving 10 of the 12 doses and was evaluable for safety.In cohort 2 (0.05 mg/kg), 3 patients (2 with MM and 1 with DLBCL) were evaluable for safety. Stabilization of serum monoclonal protein levels was observed in one MM patient of cohort 2. Two patients (1 with MM and 1 with DLBCL) progressed after receiving 8 of the 12 doses and were evaluable for safety.Results from ongoing pharmacokinetic studies, immunogenicity studies, and quantification of pro-inflammatory cytokines will be discussed. The planned dose levels for the third and fourth groups are 0.2 and 0.375 mg/kg, respectively. The results to date of this first-in-human clinical trial indicate that SNS01-T can be administered safely and the MTD has not yet been reached (Clinical Trials.gov Identifier: NCT01435720). Disclosures:Barranco:Senesco Technologies: Consultancy. Usmani:Celgene, Onyx, Millenium: Consultancy, Research Funding, Speakers Bureau. van Rhee:Jansen&Jansen: Research Funding. Thompson:Senesco Technologies: Consultancy, Equity Ownership, Membership on an entity's Board of Directors or advisory committees, Research Funding. Taylor:Senesco Technologies: stock options Other. Dondero:Senesco Technologies: Employment. Browne:Senesco Technologies Inc.: Employment, Equity Ownership, Membership on an entity's Board of Directors or advisory committees. Siegel:Celgene, Millenium, Onyx (same for all): Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau.

Efficacy and Safety of Biphasic Insulin Aspart 30/70 in Type 2 Diabetes Suboptimally Controlled on Oral Antidiabetic Therapy in Korea: A Multicenter, Open-Label, Single-Arm Study

BackgroundThe purpose of this study was to evaluate change in glycosylated hemoglobin (HbA1c), side effects, and quality of life (QOL) after a 16-week treatment period with Biphasic insulin aspart 30/70 (BIasp30) in patients with type 2 diabetes mellitus (T2DM) who had been suboptimally controlled with oral antidiabetic drugs (OADs).MethodsThe study consisted of a 4-week titration period when concurrent OAD(s) were replaced with BIasp30 and followed by a 12-week maintenance period. All patients completed the Diabetes Treatment Satisfaction Questionnaire at the beginning and the end of the trial. Hypoglycemic episodes were recorded by the patient throughout the trial.ResultsSixty patients were included, of whom 55 patients (92%) completed the full 16-week treatment period. Seven-point blood glucose was significantly improved as compared with the baseline, except for the postlunch blood glucose level. HbA1c at the end of period was significantly improved from 9.2% to 8.2% (P<0.001). Eleven percent (n=6) of patients achieved HbA1c values ≤6.5% and 22% (n=12) of patients achieved <7.0%. There were 3.4 episodes/patients-year of minor hypoglycemia and 0.05 episodes/patients-year of major hypoglycemia. QOL showed significant changes only in the acceptability of high blood glucose category (P=0.003).ConclusionTreatment with once or twice daily BIasp30 may be an option for the patients with T2DM suboptimally controlled with OADs in Korea. However, considering the low number of patients achieving the HbA1c target and the high postlunch blood glucose levels, additional management with another modality may be required for optimal control.

A Structured Protocol of Evidence-Based Conservative Care Compared With Usual Care for Acute Nonspecific Low Back Pain: A Randomized Clinical Trial

Parkin-Smith GF, Norman IJ, Briggs E, Angier E, Wood TG, Brantingham JW. A structured protocol of evidence-based conservative care compared with usual care for acute nonspecific low back pain: a randomized clinical trial. Objective To compare a protocol of evidence-based conservative care with usual care for acute nonspecific low back pain (LBP) of less than 6 weeks' duration. Design Parallel-group randomized trial. Setting Three practices in the United Kingdom. Participants Convenience sample of 149 eligible patients were invited to participate in the study, with 118 volunteers being consented and randomly allocated to a treatment group. Interventions The experimental group received evidence-based treatments for acute nonspecific LBP as prescribed in a structured protocol of care developed for this study. The control group received usual conservative care. Participants in both groups could receive up to 7 treatments over a 4-week period. Main Outcome Measures Oswestry Low Back Disability Index (ODI), visual analog scale (VAS), and Patient Satisfaction Questionnaire, alongside estimation of clinically meaningful outcomes. Results Total dropout rate was 14% (n=16), with 13% of data missing. Missing data were replaced using a multiple imputation method. Participants in both groups received an average of 6 treatments. There was no statistically significant difference in disability (ODI) scores at the end of week 4 ( P= .33), but there was for pain (VAS) scores ( P< .001). Interestingly, there were statistically significant differences between the 2 groups for both disability and pain measures at the midpoint of the treatment period ( P< .001). Patient satisfaction with care was equally high (85%) in both groups. Minimally clinically important differences in scores and number needed to treat scores (NNT<6) indicated that the experimental treatment (protocol of care) offered a clinically meaningful benefit over the control treatment (usual care), particularly at the midpoint of the treatment period. Conclusions Overall, the 2 treatment groups were similar based on primary or secondary outcome measure scores for the full treatment period (4 weeks, with up to 7 treatments). However, there were statistically significant and clinically meaningful differences in both disability and pain scores at week 2 (midpoint) with 4 treatments, suggesting that the protocol of care had a more rapid effect than usual care.

ORIGINAL ARTICLE: Effect of pioglitazone and acarbose on endothelial inflammation biomarkers during oral glucose tolerance test in diabetic patients treated with sulphonylureas and metformin

The increased risk of cardiovascular events in diabetic patients has been related to numerous metabolic and haemoreological factors. Some of these factors appear to be particularly evident during the post-prandial phases and to be related to peak plasma glucose level. To compare the effect of addition of pioglitazone and acarbose to sulphonylureas and metformin therapy on metabolic parameters and on markers of endothelial dysfunction and vascular inflammation in type 2 diabetic patients. We enrolled 473 caucasian type 2 diabetic patients. All patients underwent measurements of height and body weight, body mass index (BMI), glycated haemoglobin (HbA1c) , fasting plasma glucose (FPG), post-prandial plasma glucose (PPG), fasting plasma insulin (FPI), post-prandial plasma insulin (PPI), homeostasis model assessment (HOMA index), systolic blood pressure (SBP), diastolic blood pressure (DBP), total cholesterol (TC), low density lipoprotein-cholesterol (LDL-C), high density lipoprotein-cholesterol (HDL-C), triglycerides (Tg), sICAM-1, IL-6, high-sensitivity C reactive protein (hsCRP), sVCAM-1, sE-selectin and tumour necrosis factor (TNF-α). Assessments were made at start of titration, after 3 months [before a first oral glucose tolerance test (OGTT)], after 6 months and at the study end (before a second OGTT). Two-hundred and seventy four patients completed the study: 138 were randomized to double-blind treatment with pioglitazone and 136 with acarbose. Significant BMI and weight increase were observed after full treatment in the pioglitazone group relative to the acarbose group. A decrease in glycated haemoglobin was observed after the titration period in the pioglitazone group compared to both baseline value and the acarbose group. A decrease in glycated haemoglobin was also obtained after full treatment in the pioglitazone group when compared to the end of titration period and to the acarbose group. Significant decrease in FPG was obtained in the pioglitazone group after full treatment compared to the end of titration period. Post-prandial plasma glucose decrease was observed in acarbose group compared to the baseline value and to the end of titration period. Fasting plasma insulin decreased in the pioglitazone group after both the titration period and the full treatment period compared to both the baseline value and the acarbose group. The HOMA index decreased significantly after the full treatment in pioglitazone group compared to the end of titration period and to the acarbose group. Interleukin-6 and tumour necrosis factor-α decreased after full treatment in the pioglitazone group relative to the end of titration period. Significant hsCRP decrease was obtained after the titration period when compared to the baseline value in the pioglitazone group. High-sensitivity C reactive protein decreased in the pioglitazone group after full treatment compared to the end of titration period and to the acarbose group. Pioglitazone reduces the inflammatory response to a glucose challenge more than acarbose in type 2 diabetic patients, already treated with maximal doses of sulphonylureas and metformin.

Ribavirin dose reduction raises relapse rate dose‐dependently in genotype 1 patients with hepatitis C responding to pegylated interferon alpha‐2b plus ribavirin

The impact of ribavirin exposure on virologic relapse remains controversial in combination therapy with pegylated interferon (Peg-IFN) and ribavirin for patients with chronic hepatitis C (CH-C) genotype 1. The present study was conducted to investigate this. Nine hundred and eighty-four patients with CH-C genotype 1 were enrolled. The drug exposure of each medication was calculated by averaging the dose actually taken. For the 472 patients who were HCV RNA negative at week 24 and week 48, multivariate logistic regression analysis showed that the degree of fibrosis (P = 0.002), the timing of HCV RNA negativiation (P < 0.001) and the mean doses of ribavirin (P < 0.001) were significantly associated with relapse, but those of Peg-IFN were not. Stepwise reduction of the ribavirin dose was associated with a stepwise increase in relapse rate from 11% to 60%. For patients with complete early virologic response (c-EVR) defined as HCV RNA negativity at week 12, only 4% relapse was found in patients given > or = 12 mg/kg/day of ribavirin and ribavirin exposure affected the relapse even after treatment week 12, while Peg-IFN could be reduced to 0.6 microg/kg/week after week 12 without the increase of relapse rate. Ribavirin showed dose-dependent correlation with the relapse. Maintaining as high a ribavirin dose as possible (> or = 12 mg/kg/day) during the full treatment period can lead to suppression of the relapse in HCV genotype 1 patients responding to Peg-IFN alpha-2b plus ribavirin, especially in c-EVR patients.

Citalopram and suicidality in adult major depression and anxiety disorders

The suicide-related data on citalopram from controlled clinical trials in depression and anxiety disorders were analysed. Safety data from placebo-controlled and relapse prevention citalopram trials in depression/major depressive disorder (MDD) and anxiety were searched for specific events relating to fatal suicide, non-fatal self-harm or suicidal thoughts. Efficacy data (item 10, suicidal thoughts, on the Montgomery–Åsberg Depression Rating Scale [MADRS]) were also analysed. In the clinical trial database, the number of adverse events (fatal suicide, non-fatal self-harm or suicidal thoughts) was low, both during the first 2 weeks of treatment and during the full treatment period, with no statistically significant differences between citalopram and placebo. There was one fatal suicide during treatment (after 12 weeks of double-blind treatment in a relapse-prevention trial) for a patient treated with citalopram (incidence: 0.4%; rate: 0.010) and none on placebo. Citalopram was significantly more efficacious than placebo in lowering suicidal thoughts, based on efficacy rating (MADRS, item 10). There was no indication from this review of clinical trial data that citalopram may increase the risk of suicide in patients with MDD or anxiety. However, the patients in these clinical trials represent a selected group, as those patients with a significant risk of suicide were excluded at trial onset.

Ketotifen improves sperm motility and sperm morphology in male patients with leukocytospermia and unexplained infertility

In an open, uncontrolled study, the effect of 12 weeks of daily administration of ketotifen, an antihistamine-like drug with a mast cell stabilizing effect, on the semen quality of 55 men with leukocytospermia and unexplained infertility was examined. After 4 weeks of treatment, white blood cell count dramatically diminished and was accompanied by a significant improvement in sperm motility. A significant increase of morphologically normal sperm cells was observed at 8 weeks of treatment, and these changes remained until at least 4 weeks after the end of treatment.

Impact of adjuvant chemotherapy prior to endocrine therapy: 68 month results from the ‘Arimidex’, Tamoxifen, Alone or in Combination (ATAC) trial

608 Background: Previous analyses of the ATAC trial demonstrated initial adjuvant treatment with anastrozole (A) has significant efficacy and tolerability advantages over tamoxifen (T). At 33 months’ median follow-up there was a potential interaction with previous chemotherapy, which was less apparent at 47 months’ median follow-up. When the effects of different chemotherapy regimens were retrospectively evaluated at 47 months, the apparent interaction was limited to patients who had received cyclophosphamide, methotrexate and 5-fluorouracil (CMF). Here we evaluate the results from the ATAC trial at 68 months’ median follow-up to assess the effect of different chemotherapy regimens on time to recurrence (TTR) over the full 5-year treatment period. Methods: Chemotherapy regimens were (1) CMF, (2) anthracycline (AC)-containing regimens (AC, cyclophosphamide ± 5-fluorouracil), (3) other chemotherapies, including taxane-containing combinations. The impact of regimens on TTR was calculated and expressed as hazard ratios (HRs) with 95% confidence intervals (CIs). Results: Consistent with the 47-month analysis, superiority for TTR was maintained for A versus T in the AC-containing and taxane-containing subgroups. Advantages for A are now evident with CMF. Adjusting for chemotherapy type had only a minimal effect on TTR. Conclusions: Despite the previously reported interaction within the CMF-group, additional follow-up has confirmed that the benefits of A over T are maintained regardless of the type of chemotherapy given. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration AstraZeneca AstraZeneca

Escitalopram and suicidality in adult depression and anxiety

The escitalopram clinical trial database, consisting of all placebo-controlled and relapse prevention trials within major depressive disorder (MDD) and anxiety disorders, was analysed for specific adverse events indicative of suicidal behaviour (fatal suicide, non-fatal self-harm or suicidal thoughts) in relation to treatment. The number of events was low, with no fatal suicides in the first 2 weeks of treatment. There was one fatal suicide during the full treatment period on placebo (incidence 0.1%; rate 0.003), and none on escitalopram. None of these figures were significantly different between escitalopram (n=2277) and placebo (n=1814) patients. There was no indication that escitalopram provokes suicidal behaviour compared to placebo in either MDD or anxiety disorders. Based on efficacy ratings (Montgomery-Asberg Depression Rating Scale, item 10), escitalopram was more efficacious versus placebo in lowering suicidal thoughts from weeks 1 through 8 in the treatment of patients with MDD.

Evolução para remissão clínica completa em esclerose sistêmica

OBJETIVO: mostrar a evolução de quatro pacientes para remissão clínica completa da esclerose sistêmica (ES), sem necessidade de tratamento medicamentoso atual, após uso de D-penicilamina como medicação principal. MÉTODOS: revisão dos prontuários de pacientes com diagnóstico de ES (ARA, 1980) que entraram em remissão após acompanhamento ambulatorial continuado. Foram relacionados dados como sexo, raça, idade do paciente quando do diagnóstico, manifestações iniciais, envolvimento sistêmico, perfil laboratorial, exames complementares, tratamento proposto, resposta medicamentosa e tempo total de tratamento. RESULTADOS: todos os pacientes eram brancos, sendo um homem e três mulheres, tendo como idade média 51,2 anos na instalação dos primeiros sintomas. O tempo médio decorrido entre o início dos sintomas e o diagnóstico foi de 8,2 meses. Todos os pacientes apresentaram alterações cutâneas, comprometimento sistêmico e FAN reagente em células HEp-2. Nenhum deles apresentou os auto-anticorpos específicos para ES (anticentrômero e anti Scl-70/topo I). Depois de instituída D-penicilamina, o tempo médio de tratamento para alcançar a remissão foi de 60,7±27,4 meses. Todos se encontram atualmente sem tratamento de qualquer natureza por períodos de 31 a 120 meses e sem manifestações que indiquem atividade da ES, mesmo fenômeno de Raynaud. CONCLUSÕES: a) no espectro clínico da ES há pacientes que entram em remissão com auxílio da D-penicilamina, permanecendo assintomáticos e sem medicação por muitos anos; b) nota-se na amostra a ausência dos auto-anticorpos mais característicos da ES (anticentrômero e anti-Scl-70/topo I) em todos os casos, um achado a ser explorado em amostra maior; c) a ausência de auto-anticorpos considerados como mais específicos da ES poderia ser indicativa de melhor resposta à terapia com D-penicilamina ou de possível evolução para remissão clínica espontânea.

Zonisamide add-on for drug-resistant partial epilepsy.

The majority of people with epilepsy have a good prognosis and their seizures can be well controlled with the use of a single antiepileptic agent, but up to 30 per cent develop refractory epilepsy, especially those with partial seizures. In this review we summarize the current evidence regarding zonisamide, when used as an add-on treatment for drug-resistant partial epilepsy. To evaluate the effects of zonisamide when used as an add-on treatment for people with drug -resistant partial epilepsy. We searched the Cochrane Epilepsy Group trial register (14/12/01), the Cochrane Controlled Trials Register (Cochrane Library Issue 4, 2001). In addition, we contacted Dainippon and Elan Pharma (makers and licensees of zonisamide) and experts in the field to seek any ongoing studies or unpublished studies. Randomized placebo controlled add-on trials of zonisamide in people with drug-resistant partial epilepsy. Two reviewers independently selected trials for inclusion and extracted relevant data. Outcomes were: (a) fifty per cent or greater reduction in total seizure frequency; (b) treatment withdrawal (any reason); (c) adverse events. Primary analyses were intention to treat. Summary odds ratios (ORs) were estimated for each outcome. Three trials (499 participants) were included. The overall odds ratio (OR, 95% Confidence Interval (CI)) for 50 per cent reduction in seizure frequency compared to placebo was 2.07(1.36 to 3.15) for a 400mg/day dose of zonisamide. When the full treatment period of 12 weeks was considered for all three trials including varied rates of titration to 400mg/day the OR compared to placebo was 2.72(95% CI 1.74 to 4.25). There was insufficient evidence to support a dose response relationship for this outcome. The OR for treatment withdrawal was 1.74(95% CI 1.03 to 2.95). The 99% CI for the following side effects indicate that they are significantly associated with zonisamide: ataxia 3.94(1.23 to 12.57); somnolence 2.11(1.11 to 3.98); agitation 3.52(1.26 to 9.68); agitation and irritability 2.43(1.04 to 5.66) and anorexia 2.98(1.38 to 6.42). Zonisamide has efficacy as an add-on treatment in people with drug-resistant partial epilepsy. Minimum effective and maximum tolerated doses cannot be identified. The trials reviewed were of 12 week duration and results cannot be used to confirm longer periods of effectiveness in seizure control. The results cannot be extrapolated to monotherapy or to people with other seizure types or epilepsy syndromes.

Prognostic indicators in venous ulcers

Background: Venous ulcers can be difficult to heal, and prognostic factors for healing have not been fully elucidated. Objective: The objective of this study was to analyze the results of a large multicenter venous ulcer trial to retrospectively establish prognostic factors for venous ulcer healing. Methods: This study examined data from a previously published prospective randomized placebo-controlled trial of an oral medication versus placebo treatment for venous ulcers. Local leg ulcer care involved the use of a moisture-retentive dressing and sustained graduated compression with a paste bandage and a self-adherent wrap. The oral medication or placebo was administered on a daily basis with the same dressings and bandage system in both groups for 12 weeks. A total of 165 patients completed the full 12-week treatment period; 83 received ifetroban, 82 received placebo. Results: There was no statistically significant difference in outcome between the two groups. The study showed that consistent local ulcer treatment with a clearly defined system of care was associated with an unexpectedly high percentage (55%) of long-standing large venous ulcers (mean duration, 27 months; mean area, 15.9 cm2) being healed in both groups. Baseline ulcer area and duration of leg ulcer were found to be important in predicting outcome. Ulcers of short duration were found to be most likely to heal. Percent healing and ulcer area at week 3 were good predictors of 100% healing. Ulcers that had at least 40% healing by week 3 predicted more than 70% of the outcomes correctly. Conclusion: From this large study it was determined that baseline ulcer area and ulcer duration are significant predictors of 100% healing and time to heal. Percent healing and ulcer area at week 3 are good predictors of complete ulcer healing. Ulcers that are large, long-standing, and slow to heal after 3 weeks of optimal therapy are unlikely to heal rapidly, and might benefit from alternative therapies. (J Am Acad Dermatol 2000;43:627-30.)

The effects of lithium carbonate on healthy volunteers: Mood stabilization?

A 2-month lithium-placebo double-blind cross-over study was carried out with 17 healthy volunteers. Their mood was self-rated: twice daily ( AM, PM) with the Visual Analogue Mood Scale (VAMS); weekly with the analogue scales for subjective states and body symptoms; and three times (basal and at the end of each treatment period) with the Profile of Mood States (POMS). Memory and reaction time were also assessed, but did not show any change. The mean VAMS score decreased during lithium treatment, but the mean mood variability, a measure of the mean successive differences between consecutive mood ratings (delta squared), did not change significantly. There was a tendency toward decreased mood variability on lithium, both during the full 1-month treatment period and in the last week of treatment, when all volunteers had a lithium serum levels ranging from 0.6 to 1.0 mEq/liter. The lower mean VAMS scores on lithium could be attributed to lithium-induced dysphoric mood as recorded on the analogue scales and POMS. However, very large inter- and intraindividual differences in response to lithium were observed. Actually, lithium even had an opposite effect on some volunteers' mood. The data and problems involved with assessment of mood and its changes are discussed.

Effect of cadmium on hepatic and renal gluconeogenic enzymes in female rats

Earlier, we have reported that cadmium (Cd) induced gluconeogenesis in male rats. Since females are as much exposed to cadmium as are males, this study was conducted to determine Cd effects on gluconeogenesis in female rats. Adult female rats were injected intraperitoneally (i.p.) with Cd at dose levels of 0.25, 0.75 and 1.25 mg kg body weight per day for 4 weeks. The controls received saline for the same length of time. Daily food consumption and body weight gain were recorded. At the end of 2 and 4 weeks, 4 rats from each group were killed. Extension of treatment with 1.25 mg Cd for 4 weeks resulted in extreme Cd toxicity killing all animals before the completion of full treatment period. There were no significant changes in total body weight gain and weights of liver and kidney due to Cd. Serum protein increased significantly in animals receiving 0.75 and 1.25 mg Cd for 4 and 2 weeks, whereas serum glucose increased only in animals injected with 1.25 mg Cd for 2 weeks. SGOT and SGPT were elevated ( P < 0.01) in dose- and time-dependent fashion. Activities of three key gluconeogenic enzymes glucose-6-phosphatase (G-6-Pase), fructose-1,6-diphosphatase (FD-Pase), and phosphoenolpyruvate carboxykinase (PEPCK) in liver and kidney were induced significantly ( P < 0.01) in animals injected with 0.75 mg for 2 and 4 weeks and 1.25 mg for 2 weeks, and these increases were dose- and time-related. These results suggest that Cd alters hepatic and renal gluconeogenesis in female rats also.