scholarly journals Biological Control of The White Cochineal Parlatoria Blanchardi (Hemiptera - Diaspididae) by Using Coccidiphagous Ladybirds and Biopesticides in Palm Groves of The Region of Ouargla (South-East Algeria)

2021 ◽  
Vol 910 (1) ◽  
pp. 012034
Author(s):  
Benameur-Saggou Hayet ◽  
Rekia Chennouf ◽  
Gassou Insar ◽  
Kirouane Noureddine ◽  
Goui Khaoula ◽  
...  
Keyword(s):  
Biological Control ◽  
Azadirachta Indica ◽  
Low Dose ◽  
Date Palm ◽  
High Dose ◽  
Aqueous Extracts ◽  
Low Doses ◽  
Neem Extract ◽  
High Doses ◽  
Very High

Abstract The white cochineal of the date palm is a very serious pest in the palm groves of the Ouargla region (South-East Algeria). Our attempt at biological control of this pest was based on the use of two coccidiphagous ladybirds Pharoscymnus ovoideus and Pharoscymnus numidicus and aqueous extracts of two Saharan plants Solenostemma argel and Azadirachta indica with two doses in two palm groves in the Ouargla region. The results obtained are very encouraging. White cochineal infestation rates of treated plants decreased considerably especially for the high dose of two treatments. The infestation rate decreased from 52.54% to 35.49% with P.ovoideus (120 ladybirds/tree) and from 54.03% to 18.88% with Neem extract (dose 5%), to 11.01% with Argel extract (dose 7.5%). The two ladybirds and the two extracts used showed highly significant differences (P=0.000), as did the two doses used (P< 0.0001). Our control attempt also showed an efficiency that increased with the increase of the dose used. It is 0.119±0.20 with the low dose of P. ovoideus to reach an efficiency of 0.324±0.23. For the extract-based treatments, the highest efficacy was recorded with the high dose Argel (0.812±0.22). It should be noted that the low doses used for both treatments gave insignificant results compared to their controls with the high doses, which showed very high significant differences with P=0.000 for the ladybird releases and P<0.0001 for the high doses of the water extracts.

ANDROGENIZATION OF THE NEONATAL FEMALE RAT WITH VERY LOW DOSES OF ANDROGEN

1973 ◽  
Vol 57 (1) ◽  
pp. 33-45 ◽  
Author(s):  
P. J. SHERIDAN ◽  
M. X. ZARROW ◽  
V. H. DENENBERG
Keyword(s):  
Low Dose ◽  
Physiological Effect ◽  
Neonatal Rat ◽  
Female Rats ◽  
High Dose ◽  
Female Rat ◽  
Low Doses ◽  
Minimal Effective Dose ◽  
High Doses ◽  
Long Acting

SUMMARY The administration of a high dose of androgen on a single day to a neonatal female rat has been shown repeatedly to induce persistent vaginal cornification (PVC). However, this type of treatment does not parallel the continuous androgen secretion present in the male, and the high doses that have been used could represent a pharmacological and not a physiological effect. Experiments were carried out to determine the minimal effective dose of testosterone propionate (TP) needed to cause PVC when the androgen is administered to the neonatal rat for the first 10 days of life or as a long-acting ester. Injection of 1, 3 or 9 μg TP on days 1–10 of life in female rats induced PVC in adulthood. All three doses were found to be more effective than a testicular transplant on day 1. In female rats injected with low doses of TP twice daily for the first 10 days of life, PVC was shown between 90 and 100 days of life in 21 out of 22 animals given 0·5 μg TP/injection, and in eight out of 22 animals given 0·05 μg TP/injection. In an experiment where female rats were given a single injection of 0·1, 1·0 or 10·0 μg TP, or 0·1 or 1·0 μg testosterone cyclopentylpropionate (TC, a long-acting androgen) on the first day after birth, PVC occurred at 90–100 days of age in 15 of the 18 animals which were injected with 10 μg TP, in none of the 17 animals which were injected with 1 μg TP, and in 10 of 11 animals which were injected with 1 μg TC. The effects of all treatments on vaginal opening, first oestrus, ovarian weight, body weight and sexual behaviour are reported. The use and implications of low dose regimens are discussed in relation to the construction of an experimental model for the study of sexual differentiation.

scholarly journals The Effects of Increasing Doses of Ranitidine on Gastric pH in Children

2004 ◽  
Vol 9 (4) ◽  
pp. 259-264 ◽  
Author(s):  
Seema Khan ◽  
Theresa M. Shalaby ◽  
Susan R. Orenstein
Keyword(s):  
Low Dose ◽  
Ph Monitoring ◽  
Phase 1 ◽  
Randomized Study ◽  
Gastric Ph ◽  
Fixed Dose ◽  
High Dose ◽  
Low Doses ◽  
The Mean ◽  
High Doses

BACKGROUND Ranitidine is widely used for gastroesophageal reflux disease (GERD) in children, but optimal dosing is unclear. We compared effects of weight-based doses of oral ranitidine on gastric pH in children with clinical GERD. METHODS Children ages 4–11 years with clinical GERD were enrolled in a multi-center prospective randomized study comparing a fixed dose of ranitidine (Zantac 75) with placebo after an overnight fast; gastric pH was measured for 6 h after the fixed dose (Phase 1). Of the six enrollees from our center, four received active drug during Phase 1; 12 h after the fixed dose, these four children received ranitidine 5 mg/kg (maximum 150 mg) and gastric pH was measured for another 6–12 hours (Phase 2). This report details the effects of two dose ranges (Low Dose, &lt; 3 mg/kg/dose, and High Dose, ≥ 3 mg/kg/dose) on gastric pH in children. RESULTS The four children were 6.9–11.3 years old and weighed 20.4–49.5 kg. The Low Doses were 1.5–2.7 mg/kg; the High Doses were 3–5 mg/kg. Although the mean percentage of time with gastric pH &gt; 4 during the entire 6 hours following dosing was similar after Low and High Dose (50% vs. 57%, NS), during the last two hours of this interval the mean percentage of time with gastric pH &gt; 4 was only 29% for Low Dose vs. 89% for High Dose (P = 0.006). Moreover, during those two hours, none of the Low Doses kept gastric pH above 4 for &gt; 60% of the time, while all of the High Doses kept pH above 4 for &gt; 60% of the time (P = 0.03). In three of four patients who underwent extended (9–12 h) gastric pH monitoring after High Dose ranitidine, gastric pH was above 4 for more than 40% of total time. CONCLUSIONS Doses of ranitidine ≥ 3 mg/kg/dose may be required for acid suppression lasting beyond 6 hours.

scholarly journals MON-LB53 Prior Injectable Somatostatin Receptor Ligand Dose Does Not Predict Oral Octreotide Response In The Treatment Of Acromegaly: Results From The Phase 3 OPTIMAL Study

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Lisa B Nachtigall ◽  
Susan Leanne Samson ◽  
Maria Fleseriu ◽  
Marek Bolanowski ◽  
William Henry Ludlam ◽  
...  
Keyword(s):  
Treatment Effect ◽  
Low Dose ◽  
Somatostatin Receptor ◽  
Prior Treatment ◽  
High Dose ◽  
Low Doses ◽  
Phase 3 ◽  
Somatostatin Receptor Ligands ◽  
Igf I ◽  
High Doses

Abstract Background: Injectable somatostatin receptor ligands (SRLs) are the most widely used therapy to control acromegaly. Oral octreotide capsules have been formulated as a potential therapy for this disorder and the efficacy and safety was evaluated in the CHIASMA OPTIMAL prospective phase 3 study in patients with acromegaly who were controlled on injectable SRL treatment of varying doses (Samson et al. ENDO 2020). Methods: Patients with confirmed acromegaly, who had been receiving a stable dose of injectable SRL (≥3 months) up until study entry, were randomized to receive octreotide capsules (40 mg/day) or placebo for 36 weeks. Patients were dose titrated to 60 or 80 mg of oral octreotide or equivalent placebo through week 24 at the investigator’s discretion based on increase of IGF-I levels or worsening of acromegaly signs and symptoms. The primary efficacy endpoint was the proportion of patients who maintained their biochemical response at the end of 36 weeks, defined as average IGF-I ≤1 x ULN between Weeks 34 and 36. An analysis evaluated maintenance of response based on prior dose of injectable SRL. Prior doses of injectable SRL were categorized based on the following classifications: octreotide 10 mg every 4 weeks or lanreotide 60 mg every 4 weeks or 120 mg every 8 weeks were stratified as low; octreotide 20 mg every 4 weeks or lanreotide 90 mg every 4 weeks or 120 mg every 6 weeks were stratified as medium; octreotide 30 mg or 40 mg or lanreotide 120 mg every 4 weeks were stratified as high. Randomization was stratified based on low dose vs med/high dose and efficacy results compared for these strata. The response rates reported for the primary end point are slightly adjusted for stratification differences as prespecified in the statistical analysis plan. Results: Six patients (21.4%) in the octreotide capsule group had received prior treatment with low doses of injectable SRLs while 22 (78.6%) had received prior treatment with medium-high doses of injectable SRLs. Maintenance of response was observed in 16 patients receiving oral octreotide. This included 66.7% of patients (n=4) previously receiving low doses of injected SRLs and 54.5% of patients (n=12) on medium-high injected doses. The treatment effect was consistent irrespective of prior dose of injectable SRL (odds ratio: 5.4 in low dose and 5.9 in medium-high dose). Conclusion: The CHIASMA OPTIMAL study recruited a population receiving predominantly medium-high doses of injectable SRLs and demonstrated maintenance of response in 58% of patients. Oral octreotide treatment effect was consistent irrespective of prior dose of injectable SRL.

Use of single or multiple injections of FSH in embryo collection programmes in goats

1993 ◽  
Vol 5 (1) ◽  
pp. 49 ◽  
Author(s):  
PA Batt ◽  
ID Killeen ◽  
AW Cameron
Keyword(s):  
Factorial Design ◽  
Low Dose ◽  
Single Injection ◽  
Control Group ◽  
High Dose ◽  
Low Doses ◽  
Multiple Injections ◽  
Embryo Recovery ◽  
The Mean ◽  
High Doses

The yield of embryos from goats treated with single injections of FSH combined with low doses of PMSG was compared with that from goats treated with conventional superovulatory regimens based on multiple doses of FSH. In one experiment, 101 female goats were assigned to 10 groups. One group received six injections of FSH-P (FSH-P control); a second group received eight injections of Ovagen (Ovagen control). The remaining eight groups conformed to a 2x2x2 factorial design in which goats received a single injection of a low or high dose of either FSH-P or Ovagen in combination with a low or high dose of PMSG. All goats were run with harnessed, entire bucks. Ovaries were examined by laparoscopy and embryos were recovered from goats that had ovulated and been mated. The mean number of normal embryos collected per goat was significantly greater in the FSH-P control group in all except those groups treated with either low or high doses of PMSG combined with a low dose of Ovagen or a low dose of PMSG combined with a high dose of Ovagen. Most goats ovulated and ovulation rates were not significantly different from the mean of the FSH-P control, except for those treated with a low dose of FSH-P combined with either low or high doses of PMSG. Embryo recovery rates were significantly lower in groups treated with a high dose of PMSG combined with a high dose of either Ovagen or FSH-P, or with low doses of PMSG and FSH-P, than in the FSH-P control.(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals Quantifying prescribed high dose opioids in the community and risk of overdose

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Joe Schofield ◽  
Deborah Steven ◽  
Rebecca Foster ◽  
Catriona Matheson ◽  
Alexander Baldacchino ◽  
...  
Keyword(s):  
Risk Factors ◽  
Service Improvement ◽  
High Dose ◽  
Opioid Overdose ◽  
Opioid Prescribing ◽  
Patient Level ◽  
Strong Opioid ◽  
High Doses ◽  
Strong Opioids ◽  
Very High

Abstract Background Opioid prescribing for a range of health issues is increasing globally. The risk of fatal and non-fatal overdose is increased among people prescribed strong opioids: in high doses in the context of polypharmacy (the use of multiple medications at the same time), especially with other sedatives; and among people with multiple morbidities including cardiorespiratory, hepatic and renal conditions. This study described and quantified the prescribing of strong opioids, comorbidities and other overdose risk factors among those prescribed strong opioids, and factors associated with high/very high opioid dosage in a regional health authority in Scotland as part of a wider service improvement exercise. Methods Participating practices ran searches to identify patients prescribed strong opioids and their characteristics, polypharmacy, and other overdose risk factors. Data were anonymised before being analysed at practice and patient-level. Morphine Equivalent Doses were calculated for patients based on drug/dose information and classed as Low/Medium/High/Very High. Descriptive statistics were generated on the strong opioid patient population and overdose risk factors. The relationship between the prescribing of strong opioids and practice/patient-level factors was investigated using linear and logistic regression models. Results Eighty-five percent (46/54) of GP practices participated. 12.4% (42,382/341,240) of individuals in participating practices were prescribed opioids and, of these, one third (14,079/42,382) were prescribed strong opioids. The most common comorbidities and overdose risk factors among strong opioid recipients were pain (67.2%), cardiovascular disease (43.2%), and mental health problems (39.3%). There was a positive significant relationship between level of social deprivation among practice caseload and level of strong opioid prescribing (p < 0.001). People prescribed strong opioids tended to be older (mean 59.7 years) and female (8638, 61.4%) and, among a subset of patients, age, gender and opioid drug class were significantly associated with prescribing of High/Very High doses. Conclusions Our findings have identified a large population at potential risk of prescription opioid overdose. There is a need to explore pragmatic models of tailored interventions which may reduce the risk of overdose within this group and clinical practice may need to be tightened to minimise overdose risk for individuals prescribed high dose opioids.

scholarly journals Evaluation of the BDNF, NGF, NT3 and NT4 Genes Expressions in the Brains of Neonatal Mice with Hypothyroidism

2017 ◽  
Vol 7 (1) ◽  
pp. 171
Author(s):  
Hamid Reza Adeli Bhroz ◽  
Kazem Parivar ◽  
Iraj Amiri ◽  
Nasim Hayati Roodbari
Keyword(s):  
Dose Group ◽  
Low Dose ◽  
Pure Water ◽  
Intervention Group ◽  
Control Group ◽  
High Dose ◽  
Endocrine Glands ◽  
Blood Samples ◽  
High Doses ◽  
The Brain

Background and Aim: Thyroid is one of the endocrine glands, (T3 and T4) play a significant role in the development of prenatal brain and the following stages. The study aimed to evaluate the effect of hypothyroidism on the amount of expression of NT4, NT3, nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) in brain of one-day rat neonates with hypothyroidism.Materials and Methods: In total, 25 mature mice of Albino NMRI race were selected after mating, divided into three group, control, as well as low-dose and high-dose intervention groups. Samples of the control group received pure water during pregnancy, whereas subjects of the intervention group with low and high doses of the medication were administered with 20 mg and 100 mg methimazole powder (dissolved in 100 cc water), respectively. After child delivery, blood samples were obtained from mother mice to determine the level of T3 and T4 in blood serum. Following that, the brain of one-day mice were removed by surgery and assessed to determine the amount of expression of NT4, NT3, NGF and BDNF using the complete kit of RT-PCR.Results: Levels of T4 and T3 in the control group were 28 ug/dl and 1.59 ug/dl, respectively. In the low-dose intervention group, the amounts of the mentioned hormones were 8 ug/dl and 0.85 ug/dl, significantly, indicating a significant reduction in the expression of NT4, NT3, NGF and BDNF genes, compared to the control group. Moreover, T4 and T3 were 6 ug/dl and 0.79 ug/dl in the high-dose group, respectively, conveying a significant decrease in the expression of NT4, NT3, NGF and BDNF genes, compared to the control group (P<0.05).

scholarly journals CD8+ T Cells Mediate Recovery andImmunopathology in West Nile VirusEncephalitis

2003 ◽  
Vol 77 (24) ◽  
pp. 13323-13334 ◽  
Author(s):  
Yang Wang ◽  
Mario Lobigs ◽  
Eva Lee ◽  
Arno Müllbacher
Keyword(s):  
T Cells ◽  
Dose Group ◽  
Low Dose ◽  
Neuronal Degeneration ◽  
High Dose ◽  
West Nile ◽  
Activation Markers ◽  
High Doses ◽  
The Brain ◽  
Deficient Mice

ABSTRACT C57BL/6J mice infected intravenously with the Sarafend strain of West Nile virus (WNV) develop a characteristic central nervous system (CNS) disease, including an acute inflammatory reaction. Dose response studies indicate two distinct kinetics of mortality. At high doses of infection (108 PFU), direct infection of the brain occurred within 24 h, resulting in 100% mortality with a 6-day mean survival time (MST), and there was minimal destruction of neural tissue. A low dose (103 PFU) of infection resulted in 27% mortality (MST, 11 days), and virus could be detected in the CNS 7 days postinfection (p.i.). Virus was present in the hypogastric lymph nodes and spleens at days 4 to 7 p.i. Histology of the brains revealed neuronal degeneration and inflammation within leptomeninges and brain parenchyma. Inflammatory cell infiltration was detectable in brains from day 4 p.i. onward in the high-dose group and from day 7 p.i. in the low-dose group, with the severity of infiltration increasing over time. The cellular infiltrates in brain consisted predominantly of CD8+, but not CD4+, T cells. CD8+ T cells in the brain and the spleen expressed the activation markers CD69 early and expressed CD25 at later time points. CD8+ T-cell-deficient mice infected with 103 PFU of WNV showed increased mortalities but prolonged MST and early infection of the CNS compared to wild-type mice. Using high doses of virus in CD8-deficient mice leads to increased survival. These results provide evidence that CD8+ T cells are involved in both recovery and immunopathology in WNV infection.

scholarly journals Ripk3 Signaling Regulates Hematopoietic Stem Cell Number and Function during Stress

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 3714-3714
Author(s):  
Lei Zhang ◽  
Huacheng Luo ◽  
Jing Li ◽  
Hong-Min Ni ◽  
Mark Sellin ◽  
...  
Keyword(s):  
Inflammatory Cytokines ◽  
Low Dose ◽  
Conflicts Of Interest ◽  
Lymphoblastic Leukemia ◽  
High Dose ◽  
Low Doses ◽  
Hematopoietic Stem ◽  
Increased Risk ◽  
Leukemia Development ◽  
Serial Transplantation

Background: Among all tissues, bone marrow (BM) is the most sensitive tissue to ionizing radiation (IR)-induced acute tissue damage (ATD) and chronic long-term residual damage (LT-RD). BM failure and a significant reduction in blood cells (pancytopenia) often occurs within days after exposure to IR due to the massive death of proliferative hematopoietic progenitor cells (HPCs). However, due to their quiescent cell cycle status and reduced fidelity of DNA repair feature, many hematopoietic stem cells (HSCs) cannot fully eliminate such damage and enter senescence; this results in LT-RD. Abnormal dysplastic hematopoiesis is the most common LT-RD in most victims of IR, followed by an increased risk of leukemia/lymphoma development. Thus IR exposure is an established cause of BM failure and leukemia. A significant increase in the production of inflammatory cytokines is induced by IR which contributes to the pathogenesis of both ATD and LT-RD. Such inflammatory cytokines induce the activation of Ripk3-Mlkl-mediated necroptotic signaling in HSCs. However, the role of Ripk3-Mlkl signaling in IR-induced damage has not studied. Experimental procedures: The self-renewal capacity of HSCs among Ripk3-/-, Mlkl-/- and WT mice were examined and compared by serial transplantation assay. The phenotypes of ATD and LT-RD induced by different dosages of IR were compared among Ripk3-/-, Mlkl-/- and WT mice. The mechanism by which Ripk3 signaling prevents IR-induced leukemia development was studied. Results: Ripk3-Mlkl signaling is not required for hematopoiesis during homeostatic condition. However, during serial transplantation, inactivation of such signaling prevents stress-induced loss of HSCs. Interestingly, Ripk3 signaling also induces an Mlkl-independent ROS-p38-p16-mediated senescence in HSCs. Thus Ripk3-/- HSCs showed better competitive hematopoietic ability compared to Mlkl-/- and WT HSCs during serial transplantation. A sub-lethal dosage of IR (6Gy) induces Ripk3-dependent NF-κB activation and pro-survival gene expression in HSCs, which is necessary for the survival of damaged HSCs. After 6Gy IR, although DNA damage is repaired in most HSCs within 2 days, a proportion of HSCs in WT and Mlkl-/- mice fail to fully repair the damage and undergo p53-p21-dependent senescence. However such cells in Ripk3-/- mice die from apoptosis. Thus the remaining HSCs in Ripk3-/- mice should be functionally normal, while a proportion of the remaining HSCs in Mlkl-/- and WT mice remain damaged but senescent, all as demonstrated by competitive hematopoietic reconstitution assay. Multiple low-doses of IR (1.75Gy once week × 4) induce HSC exhaustion in WT mice but not in Ripk3-/- and Mlkl-/- mice. Interestingly, almost all Ripk3-/- mice develop acute lymphoblastic leukemia within 200 days after such low dose IR, while 45% of WT and 60% of Mlkl-/- mice develop thymomas within 360 days (see Figure). Mechanistically, such low-dose IR stimulates chronic inflammatory cytokine production. Such cytokines induce Ripk3-Mlkl-mediated necroptosis in response to HSC exhaustion observed in WT mice. These cytokines also induce Ripk3-ROS-p38-p16-mediated senescence in response to impaired HSC functioning observed in both WT and Mlkl-/- mice. In Ripk3-/- mice, due to the lack of both necroptotic and senescent signaling, mutant HSCs accumulate and leukemia development is accelerated. Conclusion: Ripk3 signaling plays distinct roles in HSCs in response to different doses of IR. High-dose IR induces Ripk3-dependent NF-κB/survival signaling, which is required for the survival of HSCs which fail to repair the damage. Thus temporal inhibition of Ripk3-NF-κB signaling might help to remove the damaged HSCs thus preventing the occurrence of LT-RD. However multiple low-doses of IR induces Ripk3 activation in HSCs which represses leukemia development by inducing both ROS-p38-p16-mediated senescence and Ripk3-Mlkl-mediated necroptosis. Induced activation of Mlkl-necroptosis might help to repress leukemia development by removing damaged HSCs. Disclosures No relevant conflicts of interest to declare.

scholarly journals Proteins as targets for high dilutions of drugs: Interaction between ?-amylase and mercuric chloride.

2021 ◽  
Vol 17 (2) ◽  
pp. 24-25
Author(s):  
Nirmal Chandra Sukul ◽  
Tandra Sarkar ◽  
Atheni Konar ◽  
Anirban Sukul
Keyword(s):  
Mercuric Chloride ◽  
Binding Sites ◽  
Low Dose ◽  
Soluble Starch ◽  
Low Doses ◽  
Substrate Interaction ◽  
Enzyme Substrate ◽  
High Dilutions ◽  
High Doses ◽  
Mother Tincture

Background: High dilutions of drugs, used in homeopathy, are usually applied by oral route or foliar spray. These dilutions first come in contact with membrane or circulating proteins. Ultra low doses of mercuric chloride, called potencies, promote activity of diastase or ?-amylase in terms of breakdown of starch, a polysaccharide into a disaccharide maltose in a cell-free medium in test tubes. Merc cor or HgCl2 in high doses inhibits the enzyme activity. Aims: To see (i) whether the high and ultra low dose effects of HgCl2 involve different binding sites of the enzyme and (ii) to find an explanation for the low dose effect of HgCl2 in spite of absence of its original molecules. Methodology: Merc cor mother tincture (147 mM HgCl2) in distilled water was used undiluted in this experiment. Merc cor 200c and 1000c were prepared from the mother tincture (MT) by successive dilution with water 1:100 followed by succussion in 200 and 1000 steps, respectively, and finally preserved in 90% EtOH. These potencies and blank 90% ethanol, were diluted with deionized, distilled (DD) water 1:1000 to minimize ethanol content in test solutions. Each test solution or control was mixed with the enzyme 1:10 just before experiment. The control consisted of DD water. An isothermal calorimetry (ITC) instrument was used to measure the interaction between soluble starch and ?-amylase mixed with each potency (200c/1000c) of Merc cor, its mother tincture, ethanol and control. ITC is a thermodynamic technique which helps in measuring directly very small amount of heat evolved during chemical reaction. Soluble starch 90 µM was injected into 300 µl of 15µM ?-amylase at 2 µl / injection. Twenty injections, one every 2 min, were given. The enzyme substrate interaction in terms of heat released (exothermic) or absorbed (endothermic) were monitored by the ITC instrument. All ITC measurements were calculated and analyzed statistically by an in-built software Origin 7. Results and discussion: The data are presented in figures. While Merc cor MT shows endothermic reaction, all its potencies, ethanol and water control show exothermic reactions. There is wide variation in enthalpy (?H), entropy (?S), binding constant (K) and Gibbs free energy change (?G) among the treatments with Merc cor MT, potencies, ethanol and also control. The results indicate that Merc cor MT and its potencies act on different binding sites of the enzyme. The variation in thermodynamic parameters suggest difference in binding interaction between the drug solutions and the enzyme. This in turn influences the enzyme substrate interaction as reported in earlier studies. The potencies are virtually water modified by the starting substance HgCl2. Conclusion: The mother tincture and potencies of mercuric chloride produce different effects on the enzyme substrate interaction. Potencies show wide variation in ?H, ?S, K and ?G values. It appears from the results that the drugs used in homeopathy produce dual action on proteins. At high doses they act on a binding site(s) but at ultra low doses they act on a different binding site(s). Proteins in an organism may serve as targets for initiation of action of homeopathic potencies.

scholarly journals Toll-Like Receptor Signaling in Airborne Burkholderia thailandensis Infection

2009 ◽  
Vol 77 (12) ◽  
pp. 5612-5622 ◽  
Author(s):  
T. Eoin West ◽  
Thomas R. Hawn ◽  
Shawn J. Skerrett
Keyword(s):  
Low Dose ◽  
Inflammatory Responses ◽  
High Dose ◽  
Tlr Signaling ◽  
Necrosis Factor Alpha ◽  
Airborne Infection ◽  
Essential Components ◽  
High Doses

ABSTRACT Melioidosis is a tropical disease endemic in southeast Asia and northern Australia caused by the gram-negative soil saprophyte Burkholderia pseudomallei. Although infection is often systemic, the lung is frequently involved. B. thailandensis is a closely related organism that at high doses causes lethal pneumonia in mice. We examined the role of Toll-like receptors (TLRs), essential components of innate immunity, in vitro and in vivo during murine B. thailandensis pneumonia. TLR2, TLR4, and TLR5 mediate NF-κB activation by B. thailandensis in transfected HEK293 or CHO cells. In macrophages, TLR4 and the adaptor molecule MyD88, but not TLR2 or TLR5, are required for tumor necrosis factor alpha production induced by B. thailandensis. In low-dose airborne infection, TLR4 is needed for early, but not late, bacterial containment, and MyD88 is essential for control of infection and host survival. TLR2 and TLR5 are not necessary to contain low-dose infection. In high-dose airborne infection, TLR2 deficiency confers a slight survival advantage. Lung and systemic inflammatory responses are induced by low-dose inhaled B. thailandensis independently of individual TLRs or MyD88. These findings suggest that redundancy in TLR signaling or other MyD88-dependent pathways may be important in pneumonic B. thailandensis infection but that MyD88-independent mechanisms of inflammation are also activated. TLR signaling in B. thailandensis infection is substantially comparable to signaling induced by virulent B. pseudomallei. These studies provide additional insights into the host-pathogen interaction in pneumonic Burkholderia infection.

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