Traditional Chinese medicine on treating splenomegaly due to portal hypertension in cirrhosis: A protocol for systematic review and meta-analysis.

BACKGROUND: Liver cirrhosis is a common clinical chronic progressive disease. Due to the obstruction of blood flow after cirrhosis, it leads to long-term congestion of splenic sinus, hyperplasia of fibrous tissue and proliferation of splenic myeloid cells, resulting in hepatocirrhosis and splenomegaly. At present, western medicine still uses splenectomy and interventional therapy are the main treatment, but the adverse reactions are more and the curative effect is not good. Many clinical trials have proved that Traditional Chinese medicine has a great therapeutic effect on Hepatocirrhosis with splenomegaly, which can effectively delay the development of the disease and improve the survival rate of patients. This systematic review aims to evaluate the efficacy and safety of Traditional Chinese medicine in the treatment of hepatocirrhosis with splenomegaly. METHODS: The databases of Pubmed, CENTRAL (The Cochrane Central Register of Controlled Trials), China National Knowledge Infrastructure (CNKI), Wanfang Data Knowledge Service Platform (WANFANG Data), Weipu Information Chinese Periodical Service Platform (VIP), and China Biomedical Literature Service System (SinoMed) will be searched online to collect randomized controlled trials related to the treatment of hepatocirrhosis with splenomegaly with Traditional Chinese medicine The time is limited from the construction of the library to November 2020. We will use the criteria provided by Cochrane 5.1.0 for quality assessment and risk assessment of the included studies, and use the Revman 5.3 and Stata 13.0 software so as to systematically review the effectiveness of Traditional Chinese medicine for hepatocirrhosis with splenomegaly. ETHICS AND DISSEMINATION: This systematic review will evaluate the efficacy and safety of Traditional Chinese medicine for hepatocirrhosis with splenomegaly. Because all data used in this systematic review and meta-analysis have been published, this review does not require ethical approval. In addition, all data will be analyzed anonymously during the review process. RESULTS: In this study, we will evaluate the efficacy of Traditional Chinese medicine in the treatment of cirrhosis with splenomegaly. CONCLUSION: The conclusion of this study will be evidence to ensure the efficacy of Traditional Chinese medicine© in the treatment of cirrhosis with splenomegaly and provide guidance for its treatment. TRIAL REGISTRATION NUMBER: INPLASY2020110121.

Deciphering the multi-scale mechanisms of Tephrosia purpurea against polycystic ovarian syndrome (PCOS) and its major psychiatric comorbidities: Studies from network pharmacological perspective.

Tephrosia purpurea (T. purpurea), a plant belonging to Fabaceae (pea) family, is a well-known Ayurvedic herb and commonly known as Sarapunkha in traditional Indian medicinal system. Described as "Sarwa wranvishapaka", i.e. having a capability to heal all types of wounds, it is particularly recognized for its usage in splenomegaly. Towards exploring the comprehensive effects of T. purpurea against polycystic ovarian syndrome (PCOS) and three comorbid neuropsychiatric diseases (anxiety, depression, and bipolar disorder), its constituent phytochemicals (PCs) were extensively reviewed and their network pharmacology evaluation was carried out in this study. The complex regulatory potential of its 76 PCs against PCOS is enquired by developing and analyzing high confidence tripartite networks of protein targets of each phytochemical at both pathway and disease association scales. We also developed a high-confidence human Protein-Protein Interaction (PPI) sub-network specific to PCOS, explored its modular architecture, and probed 30 drug-like phytochemicals (DPCs) having multi-module regulatory potential. The phytochemicals showing good binding affinity towards their protein targets were also evaluated for similarity against currently available approved drugs present in DrugBank. Multi-targeting and synergistic capacities of 12 DPCs against 10 protein targets were identified and evaluated using molecular docking and interaction analyses. Eight DPCs as a potential source of PCOS and its comorbidity regulators are reported in T. purpurea. The results of network-pharmacology study highlight the therapeutic relevance of T. purpurea as PCOS-regulator and demonstrate the effectiveness of the approach in revealing action-mechanism of Ayurvedic herbs from holistic perspective.

Ethanolic extract of Salacia nitida root bark ameliorates lipid peroxidation and hepatosplenomegaly in Plasmodium berghei-malaria infected mice.

The root bark of Salacia nitida L.benth (celastraceae) is used as remedy for malaria and typhoid fever in Southern part of Nigeria. This study is designed to evaluate the effect of treatment with ethanolic extract from root bark of S. nitida on lipid peroxidation, hepatomegaly and splenomegaly in Plasmodium berghei-malaria infected mice. Thirty malaria-infected and six uninfected mice were used for the study. 280, 430, and 580 mg kg-1 body weight day-1 of ethanolic extract and 4 mg kg-1 body weight day-1 of artesunate were administered orally to infected mice in groups B, C, D, and E, while 4 ml kg-1 body weight day-1 of physiological saline was given to infected untreated mice in group A and the uninfected untreated mice in group F. Treatments were done for five days. Levels of malondialdehyde were measured as means of assessing lipid peroxidation in the experimental animals. Weights of experimental animals, liver, and spleen, and the length of spleen from experimental animals were also measured. Animal's liver and spleen-body weight ratios were determined. Results from the study showed significant decrease (P < 0.05) in levels of malondialdehyde, and significant increase (P < 0.05) in body weights. Also, significant decreases (P < 0.05) were seen in the weights of liver and spleen, lengths of spleen, and organ-body weight ratios of malaria-infected treated mice. Therefore, this study confirmed that ethanolic extract from root bark of S. nitida is effective in the treatment of malaria, as it is seen in its ability to attenuate lipid peroxidation and hepatosplenomegaly in mice, thus corroborating its traditional use for the treatment of malaria.

Interleukin-4 Administration or Zinc Supplementation Is Effective in Preventing Zinc Deficiency-Induced Hemolytic Anemia and Splenomegaly.

Nutritional zinc deficiency aggravates inflammation, subsequently causing anemia and splenomegaly in rats; however, the mechanism underlying such splenomegaly remains poorly understood. Therefore, in this study, we aimed to elucidate the mechanisms underlying the splenomegaly and anemia occurring in zinc-deficient rats and investigate whether these effects of zinc deficiency could be reversed by interleukin (IL)-4 administration or zinc supplementation. Five-week-old male Sprague-Dawley rats were fed a standard diet; fed a zinc-deficient diet (n = 7 each) and injected with saline or IL-4; or fed a zinc-deficient diet for 6 weeks followed by a standard diet for 4 weeks thereafter. White blood cells, segmented neutrophils, platelets, CD4+ T cells, CD11b/c+ granulocytes, CINC/GRO+ cells, and myeloperoxidase-positive cells in the blood and spleen of the zinc-deficient rats were significantly higher than those in all the other groups. Conversely, red blood cells, hemoglobin, hematocrit, mean corpuscular volume, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration, lymphocytes, and CD8+ T cells in the blood of the zinc-deficient rats were significantly lower than those in the other groups. Furthermore, serum aspartate aminotransferase, lactate dehydrogenase, indirect bilirubin concentrations, and erythrocyte osmotic fragility in the zinc-deficient rats were significantly higher than those in the other groups. Moreover, zinc deficiency significantly decreased the GATA1 protein levels in the spleen. Collectively, these results indicate that zinc deficiency aggravates the inflammatory response and causes hemolytic anemia and splenomegaly. Importantly, IL-4 administration and zinc supplementation can reverse the zinc deficiency-induced hemolytic anemia and splenomegaly.

Dietary Indole-3-Carbinol Alleviated Spleen Enlargement, Enhanced IgG Response in C3H/HeN Mice Infected with Citrobacter rodentium.

Enteropathogenic and enterohemorrhagic Escherichia coli are important enteric pathogens that induce hemorrhagic colitis or even fatal hemolytic uremic syndrome. Emerging evidence shows that some bio-actives derived from fruits and vegetables may serve as alternatives to antibiotics for overcoming multidrug resistant E. coli infections. In this study, the Citrobacter rodentium (Cr) infection model was utilized to mimic E. coli-induced acute intestinal inflammation, and the effects of a cruciferous vegetable-derived cancer protective compound, indole-3-carbinol (I3C), on the immune responses of Cr-susceptible C3H/HeN mice were investigated. Dietary I3C significantly inhibited the loss of body weight and the increase in spleen size in Cr infected mice. In addition, I3C treatment reduced the inflammatory response to Cr infection by maintaining anti-inflammatory cytokine IL-22 mRNA levels while reducing expression of other pro-inflammatory cytokines including IL17A, IL6, IL1ß, TNF-α, and IFN-γ. Moreover, the serum cytokine levels of IL17, TNF-α, IL12p70, and G-CSF also were down-regulated by I3C in Cr-infected mice. Additionally, dietary I3C specifically enhanced the Cr-specific IgG response to Cr infection. In general, dietary I3C reduced the Cr-induced pro-inflammatory response in susceptible C3H/HeN mice and alleviated the physiological changes and tissue damage induced by Cr infection but not Cr colonization.

Enzyme replacement and substrate reduction therapy for Gaucher disease.

BACKGROUND: Gaucher disease, a rare disorder, is caused by inherited deficiency of the enzyme glucocerebrosidase. It is unique among the ultra-orphan disorders in that four treatments are currently approved by various regulatory authorities for use in routine clinical practice. Hitherto, because of the relatively few people affected worldwide, many of whom started therapy during a prolonged period when there were essentially no alternatives to imiglucerase, these treatments have not been systematically evaluated in studies such as randomized controlled trials now considered necessary to generate the highest level of clinical evidence. OBJECTIVES: To summarize all available randomized controlled study data on the efficacy and safety of enzyme replacement therapies and substrate reduction therapy for treating Gaucher disease. SEARCH METHODS: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Inborn Errors of Metabolism Trials Register. Additional searches were conducted on ClinicalTrials.gov for any ongoing studies with potential interim results, and through PubMed. We also searched the reference lists of relevant articles and reviews.Date of last search: 07 August 2014. SELECTION CRITERIA: All randomized and quasi-randomized controlled studies (including open-label studies and cross-over studies) assessing enzyme replacement therapy or substrate reduction therapy, or both, in all types of Gaucher disease were included. DATA COLLECTION AND ANALYSIS: Two authors independently assessed the risk of bias in the included studies, and extracted relevant data. MAIN RESULTS: Of the 488 studies retrieved by the electronic searches, eight met the inclusion criteria and were analysed (300 participants). Response parameters were restricted to haemoglobin concentration, platelet count, spleen and liver volume and serum biomarkers (chitotriosidase and CCL18). Only one publication reported a 'low risk of bias' score in all parameters assessed, and all studies included were randomized.Four studies reported the responses to enzyme replacement therapy of previously untreated individuals with type 1 Gaucher disease. Two studies investigated maintenance enzyme replacement therapy in people with stable type 1 Gaucher disease previously treated for at least two years. One study compared substrate reduction therapy, enzyme replacement therapy and a combination thereof as maintenance therapy in people with type 1 Gaucher disease previously treated with enzyme replacement therapy. One study examined substrate reduction therapy in people with chronic neuronopathic (type 3) Gaucher disease who continued to receive enzyme replacement therapy.Treatment-naïve participants had similar increases in haemoglobin when comparing those receiving imiglucerase or alglucerase at 60 units/kg, imiglucerase or velaglucerase alfa at 60 U/kg, taliglucerase alfa at 30 units/kg or 60 units/kg, and velaglucerase alfa at 45 units/g or 60 units/kg. For platelet count response in participants with intact spleens, a benefit for imiglucerase over velaglucerase alfa at 60 units/kg was observed, mean difference -79.87 (95% confidence interval -137.57 to -22.17). There were no other significant differences in platelet count response when comparing different doses of velaglucerase alfa and of taliglucerase alfa, and when comparing imiglucerase to alglucerase. Spleen and liver volume reductions were not significantly different in any enzyme replacement therapy product or dose comparison study. Although a dose effect on serum biomarkers was not seen after nine months, a significantly greater reduction with higher dose was reported after 12 months in the velaglucerase study, mean difference 16.70 (95% confidence intervaI 1.51 to 31.89). In the two enzyme replacement therapy maintenance studies comparing infusions every two weeks and every four weeks, there were no significant differences in haemoglobin concentration, platelet count, and spleen and liver volumes over a 6 to 12 month period when participants were treated with the same cumulative dose.A total of 25 serious adverse events were reported, nearly all deemed unrelated to treatment.There are, as yet, no randomized trials of substrate reduction therapy in treatment-naïve patients that can be evaluated. Miglustat monotherapy appeared as effective as continued enzyme replacement therapy for maintenance of hematological, organ and biomarker responses in people with type 1 Gaucher disease previously treated with imiglucerase for at least two years. In those with neuronopathic Gaucher disease, no significant improvements in haemoglobin concentration, platelet count or organ volumes occurred when enzyme replacement therapy was augmented with miglustat.One randomized controlled study assessing substrate reduction therapy was published immediately prior to producing the final version of this review, and this, along with a further ongoing study (expected to be published in the near future), will be assessed for eligibility in a future update of the review. AUTHORS' CONCLUSIONS: The results reflect the limitations of analysing evidence restricted to prospective randomized controlled trials, especially when dealing with chronic rare diseases. This analysis suggests that, during the first year of treatment, different recombinant glucocerebrosidases are bio-similar and non-inferior in safety and efficacy for surrogate biological response parameters. Enzyme replacement therapy given at 30 to 45 units/kg body weight every two to four weeks was generally as effective as the 60 unit/kg dose for the assessed clinical outcomes. The analysis emphasise the need to determine whether it is realistic to carry out multi-decade prospective clinical trials for rare diseases such as type 1 Gaucher disease. With large treatment effects on the classical manifestations of the disorder, therapeutic investigations in Gaucher disease mandate innovative trial designs and methodology to secure decisive data concerning long-term efficacy and safety - with the realization that knowledge about disease-modifying actions that are sustained are of crucial importance to people with this chronic condition.

Effects of tetra-arsenic tetra-sulfide on BXSB lupus-prone mice: a pilot study.

Systemic lupus erythematosus (SLE) is an autoimmune disease of uncertain etiology that affects multiple tissues and organs. Arsenic trioxide (ATO) has been used in lupus-prone mice with a regulatory effect on immune abnormality. Tetra-arsenic tetra-sulfide (As4S4), a traditional Chinese medicine, is effective on acute promyelocytic leukemia with mild side effects than ATO. In this study, a pilot study was performed to investigate the effects and the mechanism of As4S4 on the lupus-prone BXSB mice. Improvement of monocytosis (p<0.05) in spleen and decreased serum interleukin-6 (IL-6) (p=0.0277) were observed with As4S4 treatment. As4S4-treated mice exhibited amelioration of skin, liver and renal disease with mild side effects. Histological analysis revealed that As4S4 suppressed immune complex deposition, mesangial proliferation and inflammatory cell infiltration in kidney and liver. Our study support that As4S4 selectively suppresses cutaneous lupus and nephritis in BXSB mice and might be a potential treatment for SLE.

Gaucher disease due to saposin C deficiency, previously described as non-neuronopathic form--no positive effects after 2-years of miglustat therapy.

Gaucher disease occurs mainly as a result of a deficiency of the lysosomal enzyme beta-glucocerebrosidase activity. A rare variant form of Gaucher disease is known in which saposin C required for glucosylceramide degradation is deficient. In an earlier paper we described the first cases of two siblings with the non-neuronopathic form of Gaucher disease caused by saposin C deficiency [Tylki-Szymanska et al., 2007]. In this article, we present a follow up of clinical and biochemical findings in one patient who has been treated with miglustat for two years. We observed that administration of miglustat failed to exert any favorable effect on the clinical condition, haematological parameters and glucosylceramide level in the serum. In two individuals (described in this article) very slow deterioration of the peripheral and central nervous systems was observed.

Janus kinase 2 inhibitors in myeloproliferative disorders.

IMPORTANCE OF THE FIELD: JAK2 is an obligatory kinase for the proliferation and differentiation of erythroid cells and megakaryocytes thus representing a relevant therapeutic target for agents that specifically inhibit its activity particularly in myeloproliferative disorders (MPD) harboring JAK2(V617F) mutations. AREAS COVERED IN THIS REVIEW: We discuss the physiopathology of the JAK2 signaling pathway and review clinical trials of JAK2 inhibitors for the treatment of MPD using papers and meeting abstracts published up to September 2010. WHAT THE READER WILL GAIN: This review helps in understanding the potential role of JAK2 inhibitors in MPD clinical trials and provides a comprehensive review regarding their efficacy and safety in these disorders. TAKE HOME MESSAGE: JAK2 inhibitors may prove to be useful only for suppressing disease manifestations. However, unlike drugs such as IFN which are capable of eliminating the malignant clone, JAK2 inhibitors are unable to eradicate the disease. In fact, results to date indicate that although these inhibitors reduce splenomegaly and alleviate constitutional symptoms irrespective of JAK2 mutational status, most have only a modest impact on the JAK2(V617F) allele burden. Considering the relevant risk of serious complications in patients undergoing splenectomy, these drugs could find a suitable indication in patients with myelofibrosis awaiting bone marrow transplantation.

Therapeutic potential of JAK2 inhibitors.

The discovery of an activating tyrosine kinase mutation JAK2V617F in myeloproliferative neoplasms (MPNs), polycythemia vera (PV), essential thrombocythemia (ET) and primary myelofibrosis (PMF) has resulted in the development of JAK2 inhibitors, of which several are being evaluated in phase I/II clinical studies. It is important to recognize that because the V617F mutation is localized in a region outside the adenosine triphosphate (ATP)-binding pocket of JAK2 enzyme, ATP-competitive inhibitors of JAK2 kinase (like the current JAK2 inhibitors in the clinic) are not likely to discriminate between wild-type and mutant JAK2 enzymes. Therefore, JAK2 inhibitors, by virtue of their near equipotent activity against wild-type JAK2 that is important for normal hematopoiesis, may have adverse myelosuppression as an expected side effect, if administered at doses that aim to completely inhibit the mutant JAK2 enzyme. While they may prove to be effective in controlling hyperproliferation of hematopoietic cells in PV and ET, they may not be able to eliminate mutant clones. On the other hand, JAK inhibitors may have great therapeutic benefit by controlling the disease for patients with MPNs who suffer from debilitating signs (eg, splenomegaly) or constitutional symptoms (which presumably result from high levels of circulating cytokines that signal through JAK enzymes). Indeed, the primary clinical benefits observed so far in MF patients have been significant reduction is splenomegaly, elimination of debilitating disease-related symptoms, and weight gain. Most importantly, patients with and without the JAK2V617F mutation appear to benefit to the same extent. In this review we summarize current clinical experience with JAK2 inhibitors in MPNs.

Therapeutic goals in Gaucher disease.

Evidence-based therapeutic goals have been developed by several European and American experts in Gaucher disease in order to attempt to reverse the entire Type 1 Gaucher phenotype, prevent complications, improve quality of life and prevent life-threatening complications. Patients with Gaucher disease will benefit by maximum enzyme replacement treatment (ERT) efficiency if it is given at the optimal time i.e. generally during the asymptomatic phase of the disease. Currently, Cerezyme is the standard of care for all severities of type 1 Gaucher disease due to its high efficiency at ameliorating bleeding tendencies, reversing organomegaly and part of skeletal damages and eliminating bone crises. ERT has also demonstrated a remarkable safety profile with tolerability at 3 years greater than 99%. Treatment of Gaucher disease is a long-life treatment that the patient should not interrupt without a careful monitoring of the disease evolution.

Tinospora cordifolia as an adjuvant drug in the treatment of hyper-reactive malarious splenomegaly--case reports.

BACKGROUND & OBJECTIVE: The effect of aqueous extract of Tinospora cordifolia, an immunomodulator with antimalarial activity along with chloroquine was studied in the treatment of three cases of hyper-reactive malarious splenomegaly in District Hospital, Daltonganj town, Jharkhand, India. These cases were partial/slow responders to the conventional antimalarial drug chloroquine. METHODS: Aqueous extract of T. cordifolia (500 mg) was added to chloroquine (CQ) base (300 mg) weekly and CQ prophylaxis was observed up to six months. Improvement was gauzed by measuring spleen enlargement, Hb, serum IgM and well-being in three cases of hyper-reactive malarious splenomegaly. RESULTS: Addition of extract of T. cordifolia for the first six weeks to chloroquine showed regression of spleen by 37-50% after six weeks and 45-69% after six months from the start of treatment. Likewise decrease in IgM and increase in Hb as well as wellbeing (Karnofsky performance scale) were observed. CONCLUSION: The results of the present study paves a new sight in the treatment of hyper-reactive malarious splenomegaly, however, large-scale trial is required to confirm the beneficial effect of T. cordifolia extract in combination with chloroquine.

Effect of selenium supplementation on mice infected with LP-BM5 MuLV, a murine AIDS model.

LP-BM5 Murine leukemia virus (MuLV) infection of C57BL/6 mice develop a disease that has many features in common with human acquired immunodeficiency syndrome (AIDS), in particular abnormal lymphoproliferation and severe immunodeficiency. Thus, this MAIDS model may be useful for evaluation of potent antirival agents in vivo. Deficiency in antioxidant micronutrients such as selenium, zinc, and glutathione have been observed in AIDs and AIDS-related complex (ARC) patients. In the present study, the MAIDS model was used to evaluate immunological and oxidative effect of Se as sodium selenite. Results indicated that Se treatment 0.1 mg/kg/d (p.o.) inhibited splenomegaly and sera IgG elevation effectively. In addition to abnormal immunity, oxidative imbalance possibly existed in MAIDS model, as lipid peroxide increased significantly in spleen and whole blood glutathione peroxidase (GSH-Px) activity decreased markedly. Se supplementation had good protective effect.

Therapeutic effects of glycyrrhizin in mice infected with LP-BM5 murine retrovirus and mechanisms involved in the prevention of disease progression.

Glycyrrhizin (GL), a plant extract, has been evaluated for its inhibitory effect on HIV replication in vitro and for its improvement of clinical symptoms in HIV-infected patients. In this study, we used GL in a murine AIDS model (MAIDS) to evaluate these effects. C57BL/6 mice were inoculated with LP-BM5 murine leukemia virus to cause MAIDS. Treatment with GL supplemented with glycine and cysteine (Stronger Neo-Minophagen C, SNMC) was then begun on day 0 or 4 wks after virus inoculation. SNMC was administered three times a week for up to 19 wks. Immunological abnormalities were monitored with respect to the surface phenotype identified by two-color staining for CD3 and IL-2 receptor beta-chain. All mice infected with the virus alone developed MAIDS and died by 14 wks after infection. The immunopathogenesis was estimated to be an abnormal expansion of intermediate CD3 cells (i.e., extrathymic T cells) as well as other types of lymphocytes. SNMC did not change the total mortality rate. However, some mice that began the treatment on day 0 or 4 wks after infection survived 3 wks longer. Splenomegaly and lymphadenopathy in such mice were suppressed. These mice showed normal phenotypic features and normal responses to Con A. These results suggest that SNMC is effective in some MAIDS mice in preventing the progression of disease. When lymphocytes isolated from the liver, spleen and lymph nodes of diseased mice were cultured in vitro, they showed a spontaneous proliferation. Interestingly, such proliferation was inhibited by addition of liver lymphocytes, but not splenic lymphocytes, obtained from normal or SNMC-treated mice. Since liver lymphocytes contains intermediate CD3 cells with autoreactivity, they may possibly suppress the progression of disease.

In vitro and in vivo activities of levofloxacin against Mycobacterium tuberculosis.

In tests with 18 drug-susceptible strains of Mycobacterium tuberculosis, the MIC at which 50% of the strains are inhibited by levofloxacin (LVFX) was one dilution less than that at which 50% of the strains are inhibited by ofloxacin (OFLO), but the MICs at which 90% of the strains are inhibited were similar. The in vivo activity of LVFX against M. tuberculosis was compared with the activities of isoniazid, OFLO, and sparfloxacin (SPFX). Mice were inoculated intravenously with 1.74 x 10(6) CFU of H37Rv, and treatments began the next day and were carried out six times weekly for 4 weeks. The severity of infection and effectiveness of treatment were assessed by survival rate, spleen weights, gross lung lesions, and enumeration of CFU in the spleen. In terms of CFU counts, the ranking of the anti-M. tuberculosis activities of the treatments used ran in the following order: LVFX (300 mg/kg of body weight) = SPFX (100 mg/kg) > isoniazid > SPFX (50 mg/kg) > OFLO (300 mg/kg) = LVFX (150 mg/kg) > OFLO (150 mg/kg) = LVFX (50 mg/kg). It seems, therefore, that the in vivo activity of LVFX is comparable to that produced by a twofold-greater dosage of OFLO. It is assumed that the maximal clinically tolerated dosage of LVFX is similar to that of OFLO, i.e., 800 mg daily, which is equivalent to 300 mg of LVFX per kg in mice. Because LVFX displayed powerful bactericidal activity, promising effects against human tuberculosis may be achieved if patients are treated with the maximal clinically tolerated dosage of LVFX.

Arsenic and Ayurveda.

Manufacture of an Ayurvedic arsenic-containing compound is described, which is currently in use in India to control blood counts of patients with haematological malignancies. The efficacy and side effects of this compound are evaluated in the light of the fact that arsenic was recognised to be of use in the control of blood counts from patients with chronic myeloid leukaemia as long as 100 years ago, in the West.

Antineoplastic activity of cannabinoids.

Lewis lung adenocarcinoma growth was retarded by the oral administration of delta9-tetrahydrocannabinol (delta9-THC), delta8-tetrahydrocannabinol (delta8-THC), and cannabinol (CBN), but not cannabidiol (CBD). Animals treated for 10 consecutive days with delta9-THC, beginning the day after tumor implantation, demonstrated a dose-dependent action of retarded tumor growth. Mice treated for 20 consecutive days with delta8-THC and CBN had reduced primary tumor size. CBD showed no inhibitory effect on tumor growth at 14, 21, or 28 days. Delta9-THC, delta8-THC, and CBN increased the mean survival time (36% at 100 mg/kg, 25% at 200 mg/kg, and 27% at 50 mg/kg, respectively), whereas CBD did not. Delta9-THC administered orally daily until death in doses of 50, 100, or 200 mg/kg did not increase the life-spans of (C57BL/6 times DBA/2)F1 (BDF1) mice hosting the L1210 murine leukemia. However, delta9-THC administered daily for 10 days significantly inhibited Friend leukemia virus-induced splenomegaly by 71% at 200 mg/kg as compared to 90.2% for actinomycin D. Experiments with bone marrow and isolated Lewis lung cells incubated in vitro with delta9-THC and delta8-THC showed a dose-dependent (10(-4)-10(-7)) inhibition (80-20%, respectively) of tritiated thymidine and 14C-uridine uptake into these cells. CBD was active only in high concentrations (10(-4)).