Homeopathic Drug improve Metabolic Abnormalities Induced by HAART in Mice | Chapter 12 | Modern Advances in Pharmaceutical Research Vol. 1

Aims: Highly Active Antiretroviral Therapy (HAART) has changed the natural history of HIV infection, several adverse events may limit its efficacy. Antiretroviral drugs are associated with increased risk of severe hepatotoxicity. Homeopathy is a popular form of complementary and alternative medicine and is used to treat certain liver ailments. Chelidonium majus has a long history in the treatment of several diseases exhibit apoptotic activity, antioxidant and hepatic-protective effects. Current study evaluated the effect of homeopathic formulations of C. majus on metabolic alterations induced in mice subjected to HAART.

Methodology: Four-week old male Swiss Webster mice, weighing approximately 28-30 g, provided by the Central Animal Laboratory of the State University of Maringá, were used in the experiments. Five experimental groups with 10 animals each were distributed as follows: (I) animals treated with HAART diluted in 1.2 mL water gavage/day, (II) animals treated with HAART diluted in 1.2 mL water gavage/day + C. majus 6CH diluted  in water 1.0 mL once a day, added to the drinking water (1:10 mL) available ad libitum, (III) animals treated with HAART diluted in 1.2 mL water gavage/day + C. majus 12CH diluted in water 1.0 mL once a day, added to  drinking water(1:10 mL) available ad libitum, (IV) animals treated with HAART diluted in 1.2 mL water gavage/day + C. majus 30CH diluted in water 1.0 mL once a day, added to  drinking water (1:10 mL) available ad libitum, (V) non-treated animals (control group) received 1.2 mL water by gavage/day. The experimental groups were treated for 15 days. The drug in the form of mother tincture, prepared with the presses juice of the root of C. majus was mixed in equal parts of grain alcohol (PA) obtained from the  laboratory HNCRISTIANO, São Paulo, Brazil (lot 5387). The mother tincture was then diluted in 1×1012 water to obtain the homeopathic preparation 6CH, diluted in 1×1024 to obtain the homeopathic preparation 12CH and diluted in 1×1060 to obtain the homeopathic preparation 30CH. The method for drug preparation followed  the  Brazilian  Homeopathic  Pharmacopoeia.  The  dilution  was  considered  free  from  any toxicity.  Overall  clinical  evaluation  was  performed  and  serum  cholesterol,  triglycerides,  hepatic enzymes (AST and ALT) were assessed by specific methods. Results were analyzed with GraphPad Prism by Student ́s t test.

Results: Showed that the HAART group presented a weight gain lower (50%) than the control group.  Small little weight gain of animals using HAART may be related to the already known adverse effects of the antiretroviral. On the other hand, animals treated with C. majus regardless of concentration used  (6CH,  12CH  or  30CH)  presented  similar  weight  gain  when  compared  to  control.  Clinical parameters such as, body weight gain, postural pattern, piloerection and stress manipulation, results of treated animals showed that clinical C. majus had similar aspects to the control group not subjected to HAART. Results may indicate that C. majus induces a general clinical improvement in animals treated  with  HAART.  C.  majus  protects  the  liver  of  mice  from  possible  damage  caused  by antiretroviral therapy. ALT parameter showed levels which were 37.4% lower in mices treated with C. majus 6CH and 41% lower in mices treated with C. majus 30CH when compared to the group treated only with HAART. AST decreased in the group treated with C. majus 6Ch and 30CH demonstrate same levels of control.

Conclusion: Homeopathic preparations of Chelidonium majus, reduced the toxic effects of HAART in mice. Decrease in cholesterol  and triglyceride levels, higher weight gain and better AST and ALT levels  were  reported.  Evaluated  parameters  indicate  that  C.  majus  may  be  decreasing  HAART-induced hepatotoxicity.

Author(s) Details

N. A. Steiner
Department of Basic Health Sciences, State University of Maringá, Maringá, PR, Brazil.

A. L. P. P. Soares
Department of Basic Health Sciences, StateUniversity of Maringá, Maringá, PR, Brazil.

R. P. Regla
Department of Basic Health Sciences, StateUniversity of Maringá, Maringá, PR, Brazil.

M. Spack Jr
Department of Basic Health Sciences, State University of Maringá, Maringá, PR, Brazil.

A. R. T. Pupulin
Department of Basic Health Sciences, State University of Maringá, Maringá, PR, Brazil.

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Arterial Vascular Complications after Total Knee Arthroplasty Decrease the Quality of Post-op Rehabilitation (A Case Report) | Chapter 11 | Modern Advances in Pharmaceutical Research Vol. 1

Introduction: Routinely patients with hip or knee arthroplasty are transferred from acute clinic to rehabilitation department at an ever earlier stage (one week post-op). The  most  frequent  complications  after  lower  extremity  arthroplasty  are:  local  pain,  edema, contracture,  tardive  calcification,  infection,  hemorrhage,  pulmonary  embolism  and  deep  vein thrombosis. Sometimes unexpected complications can provoke a delay or even suspension of the rehabilitation.

Aims of the Study: The principal objective of the current article is to remind to the wide public the possible presence (and subsequent care) of other complications, e.g. the lower limb arteritis.

Case Presentation: The presented patient is 77 years old male. Hospitalized in our PRM Department one  week  after  operation,  with  the  objective  of post-op  orthopedic  rehabilitation after total  knee arthroplasty (for advanced gonarthrosis – genu varum with angle 4°). Arterial  Echo-Doppler  of the lower extremities: Acute thrombosis of the left femoral superficial arteria, and the left popliteal supra-articular arteria (aneurysm of 30 mm), missing images of retro & supra-articular popliteal arteriae. Urgent operation was realized for the left leg diagnosed with Arteritis: Femoro-peroneal distal by-pass graft in the intern saphenous vein with angioplasty of the distal anastomosis. After the operation, the rehabilitation process was adapted to this tardive complication.

Discussion: In every case our goal is to prevent possible complications and to assure a high quality of the rehabilitation, respectively – an improvement of the patient’s quality of care and quality of life.

Conclusion: Vascular  complications  after  joint  replacement can  postpone  or  even  interrupt  the fluency  of  the  rehab  process.  In  every  clinical  case  the  PRM  &  OT  medical  doctors  must  be immediately alerted of any suspicion for complication or significant variation in expected progression / outcomes.

Author(s) Details

Prof. Ivet Borissova Koleva
Medical University of Sofia, Bulgaria.

Dr. Frederic Milvoy
Hospital ‘St Amand Montrond, France.

Borislav Radoslavov Yoshinov
Medical Faculty of Sofia University,Bulgaria.

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Immunity and Sex Concerns on Behaviour From IgE vs IgG to sex conditioned socialization? | Chapter 10 | Modern Advances in Pharmaceutical Research Vol. 1

Aims: To find evidence that the immune response modifies behavior by regulating sex hormones.

Study Design: Experimental transversal case control study and longitudinal experimental case control study.

Place and Duration of Study: Biochemistry and Molecular Biology Chair, School of Medicine, Medical Sciences Faculty, National University of Córdoba. 2009-2015.

Methodology: Albino Swiss mice Rockefeller strain (110) weighing 30g were assigned to two experimental designs. Transversal case control physiologic solution vs or Celtis tala pollen glycoprotein T or Bovine serum albumin A evaluated in forced swimming test along the course of antibodies production. Similar study but cases were treated with spironolactone (S) and immunized as previous mice. Longitudinal case control study with cases and controls the same categories as the second study but followed and evaluated in FST. Climbing, swimming floating summing a total of 8 events and delated time to contact another mouse (CT) were recorded (seconds). Plasma IgE, IgG and testosterone (Tt) were also measured.

Results: Immunization with T increases the proportion of climbing in both sexes at day 7(C male 0.42, T male 0.72, C female 0.28, T female 0.68) and reverted at day 15 (C male 0.8, T male 0.35, C female 0.47, T female 0.43), while A increased swimming in both sexes. Since climbing is more frequent in male we treated mice with S to determine if immunization effects were mediated by testosterone and reverted the changes triggered by C. tala (day 7, ST. males 0.22, ST females 0.35, day 15 ST. male 0.23, ST. female 0.32). T caused a shortening of CT in males from day 7 to 15, S produced the opposite and ST was partly similar to T (T.male12.5 to 5, S male 8,2 to 14, ST male 11 to 4.2 in sec, T female 2.9 to 6.2, S female 7.8 to 17, ST female 13 to 9.6 sec). SA in males enhanced swimming  and  decreased  floating  while  in  female decreased  swimming  and  increased  floating.  Plasma concentration ranges of Tt (ng/mL) were: CM 0.75-6.72, TM 31.1-58.5; STM 26-29.5; females remained between 0.3-039, AM 0.75-9, AF 1-19, SAM 26.5-29, SAF 0.9-1.2.

Conclusion: The results presented in this paper support our hypothesis that immune response could modify mice FST performance and socialization post stress by regulation of testosterone levels.

Author(s) Details

SadíCossy Isasi
Cátedra de Bioquímica y Biología Molecular, Facultad de Ciencias Médicas, Universidad Nacional de Córdoba, Argentina.

Christian Jalil
Cátedra de Bioquímica y Biología Molecular, Facultad de Ciencias Médicas, Universidad Nacional de Córdoba, Argentina.

Guillermo Nicolás Giordano and Jimena Ortiz,
Catedra de Bioquimica y Biología Molecular, Facultad de Ciencias Médicas, Universidad Nacional de Córdoba, Argentina.

Prof Julio Cesar Cosiansi Bai
Cátedra de Medicina II, UNAPA Hospital Ntra. Sra. de la Misericordia, Argentina.

Juan CarlosMuiño MD
Centro Formador de la Especialidad en Alergia e Inmunología/Centro Formador Asociación Asma Alergia e Inmunología de Córdoba, Facultad de Ciencias Médicas, Universidad Nacional de Córdoba, Belgrano 1502 Córdoba, Argentina.

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Patients’ Perceptions and Attitudes towards Patient information Leaflet (PIL) | Chapter 9 | Modern Advances in Pharmaceutical Research Vol. 1

Background: Patient-tested and -friendly  information leaflets provide  sufficient, accurate, and pertinent information about prescribed and over-the-counter medications to health consumers for their safety,  enhanced  satisfaction, improved  outcomes and no medication errors across the globe. However healthcare consumers’ knowledge, attitude, behaviour and perception concerning different items of drug leaflets differ across the board.

Objective: This study aimed to explore knowledge, attitude, behaviour and perception of patients towards drug/patient information leaflets in Riyadh, capital city of Saudi Arabia.

Methods: This cross-sectional study used a self-designed reliable questionnaire for collecting relevant data about drug leaflets from purposefully selected participants (n=319) attending ambulatory clinics of a main hospital of King Fahad Medical City, Riyadh.

Results: The majority of patients were females (75%), 61% patients were between the ages of 20 to 30 years, and 58% of the participants were educated to university level. About 61% to 97% of participants agreed to knowledge, attitude and behaviour items, and only 26% patients perceived that the drug information provided by healthcare professionals suffices on its own without the drug leaflets. About 62% of the participants observed that the information in the drug leaflet is more useful than the information given verbally by healthcare professionals. The majority of patients (66% to 99%) expressed variably positive behaviour and favourable attitudes toward drug leaflet information. The participants ranked ‘indications’ (31.4%) and ‘how to use’ (26.7%) drugs as the two most important sections in drug leaflet.

Conclusion: Drug leaflets are important sources of drug information both for patients and general public globally and improve their knowledge as well as positive effects on their attitude, perception and behaviour.  Healthcare  professionals  need  to  encourage  health  consumers  to  read  the  drug leaflets which need to be patient-friendly and be written clearly in understandable lay terminology and native language. Future studies should explore and compare the knowledge base of those patients who read patient information leaflet (PIL) with those who do not read it across Arabian Gulf countries.

Author(s) Details

Saud M. Alsanad
College of Medicine, Imam Muhammad Ibn Saud Islamic University (IMSIU),Riyadh, Kingdom of Saudi Arabia.

Naseem A. Qureshi
National Center for Complementary and Alternative Medicine, Ministry of Health, Riyadh, Kingdom of Saudi Arabia.

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Toxicity Studies of the Extracts of Parkia biglobosa Stem Bark in Rats | Chapter 8 | Modern Advances in Pharmaceutical Research Vol. 1

Extracts of Parkia biglobosa stem bark is used in Nigerian traditional medicine (NTM) to treat malaria, diarrhea and pains. To establish the toxicity profile of the medicine such parameters as the lethal dose (LD50) as well as effects on body functions and organs were evaluated in albino Wistar rats. The bioactive constituents of the water and methanol extracts were also evaluated as a link to toxicity. The LD50 was greater than 5000mg/kg per oral (p.o) for both extracts.  No significant (P< 0.05) changes in body weights and vital organs of treated animals. However, at 5000mg/kg of water extract, a significant  increase  in  relative  weight  of  the  kidneys  and  hyper -cholesterolemic  effects  were observed. The extract also elicited significant increase in blood glucose level. The kidneys and livers of animals treated with P. biglobosa water extract for 14 days revealed histopathological evidence of pathological lesions. The methanol extract did not show any changes in the levels of hepatic and hematological  parameters, histopathological evidence of  pathological lesions, and  serum level of urea, uric acid, bilirubin,  creatinine and total protein concentrations. Treatment elicited hypo -cholesterolemic effects and significant reduction in blood glucose level occurred in all the groups. The phytochemical screening revealed the presence of tannins, flavonoids, saponins, terpenes, cardiac glycosides, phenols  and reducing  sugars  in the  methanol extract,  the water  extract  showed the presence of similar constituents with the absence of flavonoids and cardiac glycosides. This study has shown the toxicity characteristics of the methanol and water extracts of the stem bark P. biglobosa in short time treatment with the extracts. This study has shown the diversity in toxicity as well as the chemical constituent of the stem barks of P. biglobosa in relation to the extraction solvent. However this study provides the basis for further study on the detailed toxic and pharmacological effects of the extracts of P. biglobosa stem bark and their active component(s).

Author(s) Details

Modupe Iretiola Builders
Department of Pharmacology, Faculty of Pharmacy, Bingham University, Karu, Nigeria.

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Prodrugs-Current and Future Drug Development Strategy | Chapter 7 | Modern Advances in Pharmaceutical Research Vol. 1

The  focus  of  traditional  prodrug  approach  was  on  altering  various  physiochemical  parameters, whereas the current modern computational approach considers designing prodrugs through attaching appropriate  linkers  with  drugs  having  poor  bioavailability  which  upon  exposure  to  physiological environments release the parent active drugs in a programmable (controlled) manner resulting in an improvement of their bioavailability. With the possibility of designing prodrugs with different linkers, the release rate of the parent active drugs can be controlled. The future of  prodrug  technology  is  exciting  and  yet  challenging. Advances must be made in understanding the chemistry of many organic reactions that can be effectively utilized to enable the development of more types of prodrugs. The understanding of organic reaction mechanisms of certain processes, particularly intramolecular reactions, will be the next major milestone in this field. It is envisioned that the future of prodrug technology holds the  ability  to  create  safe and  efficacious delivery of a wide range of active small molecules and biotherapeutics. This goal can be achieved using computational chemistry methods such as ab initio, semi-empirical and density functional theory (DFT), and molecular mechanics (MM) to calculate physicochemical and molecular  properties of current marketed drugs suffer low bioavailability or/and unpleasant taste or odor.

Author(s) Details

Professor Rafik Karaman
Department of Pharmaceutical Sciences, Faculty of Pharmacy, Al-Quds University, P.O. Box 20002, Jerusalem, Palestine and Department of Science, University of Basilicata, Potenza, Italy.

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Drug Interactions: A Comprehensive Update | Chapter 6 | Modern Advances in Pharmaceutical Research Vol. 1

Possibility of occurrence of drug interactions increases with the number of drugs administered. Drug interactions can be classified in a number of ways using different basis as well as terminology. Drugs may interact with other drugs, foods, beverages, contrast media, and herbs; outside or inside the body. The term “drug-condition interaction” is sometimes used when the existing medical condition makes certain drugs potentially harmful. Knowledge of In vitro interactions is essential to avoid loss of activity of drugs before administration. Although every theoretical drug interaction may not manifest in practice, “drug interactions” is a prominent cause of adverse or undesired events related to drug administration or treatment failure. Amongst the herbs, St. John’s wort has a potential of producing significant drug interactions due to its capacity to induce metabolism of number of drugs. In vivo interactions at pharmacokinetic level affect absorption, distribution, biotransformation or excretion of drugs. Induction or inhibition of cytochrome P450 (CYP450) enzymes forms a major basis of drug interactions. As compared to induction, inhibition is a fairly rapid process. Number of precipitant drugs which inhibit the metabolism is much more than those that produce induction of enzymes; hence inhibition of metabolism may lead to serious and acute adverse events by aggravating the toxicity of substrate drugs. Role of drug transporters, especially P-glycoprotein (P-gp), in causation of drug interactions is being increasingly identified. P-gp affects absorption, distribution and excretion, and hence plays a major role in pharmacokinetic drug interactions. Additionally, P-gp works hand in hand with CYP450 enzymes. In pharmacodynamic interactions, the drugs synergise or antagonise the effects at the level of target of  action.  Clinically  beneficial  and  reparative  drug  interactions  are explored to obtain useful drug combinations. Interactions of drugs with contrast media should be remembered and carefully prevented. Extensive research has led to the development of a large number of In vitro and In vivo methods to detect and predict drug interactions.“Drug interaction softwares” is an additional and significant tool for analysis and prediction of probable drug interactions. Appropriate awareness and knowledge of possible drug interactions is crucial in prevention of harmful drug interactions and their consequences.

Author(s) Details

Dr. Madhav Mutalik (MBBS, MD (Pharmacology), MBA)
Professor and Head, Departmentof Pharmacology, D Y Patil Dental School,Pune, India.

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