Pharmaceutical Chemists Research Articles

Interplay Between Malaria, Crystalline Hemozoin Formation, and Antimalarial Drug Action and Design

This review on the interplay between malaria, antimalarial drugs, and hemozoin crystals is directed, on one hand, to biologists and pharmaceutical chemists who wish to have a broader knowledge of the crystalline state related to malaria and, on the other hand, to crystallographers and physical chemists who wish to have a simple introduction to the disease and drugs employed against it. The call for this review is dictated by various considerations, not the least being the need for new antimalarial drugs, in view of developing parasitic resistance to the commonly used ones. The increasing spread of malaria is also due to several other contributing factors; besides climatic and environmental factors, the Anopheles mosquito has become increasingly resistant to insecticides and has adapted so as to avoid * To whom correspondence should be addressed. E-mail: (I.W.) isabelle.weissbuch@weizmann.ac.il or (L.L.) leslie.leiserowitz@weizmann.ac.il. The review represents the fruits, the offshoot, one may say, that may be reaped from the experience and knowledge gleaned from a collaborative effort, extending for more than a quarter of a century, on the design and use of auxiliaries for the control of crystal nucleation, morphology, and polymorphism, the structure determination of monoand multilayer films of amphiphilic molecules by grazing incidence synchrotron X-ray diffraction at the air-liquid interface, and computational studies of molecular interactions at interfaces and in the crystal bulk. These studies have been conducted in close collaboration with Meir Lahav and with other colleagues. Chem. Rev. 2008, 108, 4899–4914 4899

Uncovering the Cause of “Phossy Jaw” Circa 1858 to 1906: Oral and Maxillofacial Surgery Closed Case Files—Case Closed

The infamous "phossy jaw" that created an epidemic of exposed bone osteonecrosis exclusively in the jaws began around 1858 and continued until 1906, with only a few cases appearing since that time. This epidemic of osteonecrosis produced pain, swelling, debilitation, and a reported mortality of 20% and was linked to "yellow phosphorous," the key ingredient in "strike-anywhere" matches. In match-making factories, workers called "mixers," "dippers," and "boxers" were exposed to heated fumes containing this compound. Related to the duration of exposure, many of these workers developed painful exposed bone in the mouth, whereas their office-based counterparts did not. The exposed bone and clinical course were eerily similar to what modern day oral and maxillofacial surgeons see due to bisphosphonates used to treat metastatic cancer deposits in bone or osteoporosis. Although yellow phosphorus has a simple chemistry of P(4)O(10), when combined with H(2)O and CO(2) from respiration and with common amino acids, such as lysine, bisphosphonates almost identical to alendronate (Fosamax; Novartis Pharmaceuticals, East Hanover, NJ) and pamidronate (Aredia; Novartis Pharmaceuticals) result. Forensic evidence directly points to conversion of the yellow phosphorus in patients with "phossy jaw" to potent amino bisphosphonates by natural chemical reactions in the human body. Thus, the cause of phossy jaw in the late 1800s was actually bisphosphonate-induced osteonecrosis of the jaws, long before clever modern pharmaceutical chemists synthesized bisphosphonates. Today's bisphosphonate-induced osteonecrosis represents the second epidemic of "phossy jaw." Case closed.

Your Prodrug Releases Formaldehyde: Should You Be Concerned? No!

The title of this commentary contains a frequently asked question whenever someone presents or proposes a prodrug strategy that releases formaldehyde as a result of bioconversion of a prodrug to parent drug. Formaldehyde, a highly water-soluble one-carbon molecule, is endogenous to cells, tissues, and body fluids. Although formaldehyde is generated and incorporated into essential metabolic processes by the human body, exposure to large amounts of formaldehyde vapor can irritate the nasal mucosa and may potentially be carcinogenic. It also gives a positive Ames test. Metabolism of both endogenous and exogenous formaldehyde involves rapid oxidation to formic acid catalyzed by glutathione dependent and independent dehydrogenases in the liver and erythrocytes. Balancing this rapid detoxification pathway is endogenous formation from normal metabolic processes and exogenous formaldehyde input, resulting in approximately 0.1 mM systemic levels. The possibility that formaldehyde released upon bioconversion of prodrugs might induce toxicity has been repeatedly stated, but no convincing evidence for this perceived toxicity has been documented in experimental studies. Therefore, as pharmaceutical chemists and not as toxicologists, we present our perspective on the apparent concern with release of formaldehyde as a by-product of in vivo bioconversion of selective prodrugs, and suggest that in comparison to the total amount of daily endogenous formaldehyde production from metabolism, and exogenous exposure from food and the environment, the amount generated by prodrugs is minute and is unlikely to cause any systemic toxicity in humans. Such an argument does not preclude formaldehyde-based toxicity assessment of a prodrug. Instead, it reduces the risk that in vivo liberation of formaldehyde will cause undue toxicity.

Molecular Basis of Prodrug Activation by Human Valacyclovirase, an α-Amino Acid Ester Hydrolase

Chemical modification to improve biopharmaceutical properties, especially oral absorption and bioavailability, is a common strategy employed by pharmaceutical chemists. The approach often employs a simple structural modification and utilizes ubiquitous endogenous esterases as activation enzymes, although such enzymes are often unidentified. This report describes the crystal structure and specificity of a novel activating enzyme for valacyclovir and valganciclovir. Our structural insights show that human valacyclovirase has a unique binding mode and specificity for amino acid esters. Biochemical data demonstrate that the enzyme hydrolyzes esters of alpha-amino acids exclusively and displays a broad specificity spectrum for the aminoacyl moiety similar to tricorn-interacting aminopeptidase F1. Crystal structures of the enzyme, two mechanistic mutants, and a complex with a product analogue, when combined with biochemical analysis, reveal the key determinants for substrate recognition; that is, a flexible and mostly hydrophobic acyl pocket, a localized negative electrostatic potential, a large open leaving group-accommodating groove, and a pivotal acidic residue, Asp-123, after the nucleophile Ser-122. This is the first time that a residue immediately after the nucleophile has been found to have its side chain directed into the substrate binding pocket and play an essential role in substrate discrimination in serine hydrolases. These results as well as a phylogenetic analysis establish that the enzyme functions as a specific alpha-amino acid ester hydrolase. Valacyclovirase is a valuable target for amino acid ester prodrug-based oral drug delivery enhancement strategies.

Pharmacists lend a hand

When I read Douglas Fleming's suggestion (Pharmaceutical Journal 2007; 279: 441) that Britain's pharmacists could “play an extended role in the management of seasonal influenza”, I reacted sceptically. Pharmaceutical chemists do tend to have exaggerated ideas of their own importance. Some years ago, the Royal Pharmaceutical Society tried to restrict the sale of over-the-counter nostrums to places within its own fiefdom. Aspirin, for example, should be banned from filling stations and be made available only through pharmacies with pharmacists “in attendance”. Much more recently, Alison White, Chief Executive of the National Pharmacy Association, was grumbling about her profession being excluded from Lord Darzi's review of the UK National Health Service (The Times, Oct 26, 2007).

An investigation into analyzing patents by chemical structure using Thomson’s Derwent World Patent Index codes

Patent mapping usually involves an analysis of standard bibliometric measures such as inventors, patent assignees, patent countries, patent years or dates, and, of course, activities or uses found in the patents. In addition to these, of great importance to pharmaceutical chemists are the chemical structures patented and how they relate to the above measures. This article reviews our attempts to analyze pharmaceutical patents utilizing the chemical structure information provided in Thomson’s Derwent World Patent Index (DWPI).

The role of UHPLC in pharmaceutical development

Pharmaceutical separations can be divided into three categories: high throughput, high productivity, and high resolution. These categories contain specific pharmaceutical applications, each of which has distinct separation goals. Traditionally, these goals have been achieved utilizing conventional HPLC with typical column dimensions and particle sizes. The recent introduction of ultra-HPLC (UHPLC) has provided a new potential for method development and analysis. Pharmaceutical chemists must determine the impact of this emerging technology. UHPLC is achieved by using sub-2 microm particle size column packing at increased linear velocities. In order to utilize this technology, mobile phase viscosity must be minimized or the chromatography system must be redesigned to withstand an increased backpressure. Today, there are many commercially available UHPLC systems capable of exceeding conventional pressure limits of 400 bar. The advantage of UHPLC over conventional HPLC is the capability to increase the speed without sacrificing efficiency. In comparison to traditional HPLC, our research showed that UHPLC can decrease run times up to 7 x. In addition, for high resolution applications, UHPLC achieved significant efficiency advantages over traditional HPLC. This paper will evaluate the potential roles for utilizing UHPLC in the pharmaceutical industry.

Meeting Report: Targeting the Kinome—20 Years of Tyrosine Kinase Inhibitor Research in BaselA report on the "Targeting the Kinome" meeting, Basel, Switzerland, 4 to 6 December 2006.

With basic and pharmaceutical researchers, chemists, pharmacologists, and clinicians, the Targeting the Kinome meeting brought together a tremendous group of scientists to discuss the past, present, and future of protein kinase research, with a special emphasis on cancer therapy development. The topics ranged from the kinases themselves as drug targets through the interactions that the actions of these enzymes promote, to the physiological and pathological processes they regulate. Attendees gained insight into drug development, as well as increased understanding of how normal cellular processes are subverted during oncogenesis, which may lead to new targets for intervention.

Possible effects of phthalate exposure in doses relevant for humans

Possible effects of phthalate exposure in doses relevant for humans

Special Issue Preface, DNA Based Sensors

first_page settings Order Article Reprints Font Type: Arial Georgia Verdana Font Size: Aa Aa Aa Line Spacing:    Column Width:    Background: Open AccessEditorial Special Issue Preface, DNA Based Sensors by Jan Labuda Department of Analytical Chemistry, Faculty of Chemical and Food Technology, Slovak University of Technology, 81237 Bratislava, Slovakia Sensors 2005, 5(6), 343; https://doi.org/10.3390/s5060343 Published: 13 November 2005 (This article belongs to the Special Issue DNA Based Sensors) Download Download PDF Download PDF with Cover Download XML Download Epub Versions Notes DNA-based sensors belong to chemical sensors used in chemical/biochemical analysis. Among the biosensors generally, there are some specific features at these sensors regarding their use to the investigation of DNA itself, both its amount (concentration) and chemical/biochemical reactivity. With respect to this, the DNA biosensors represent irreplaceable testing devices. From the discovery of electrochemical activity of nucleic acids by Palecek at the end of the 1950‘s, huge progress can be observed, particularly at the development of electrochemical DNA biosensors based on the concept of chemically modified electrodes. Together with an economic prospect, these devices have already achieved extremely high analytical sensitivity detecting, for instance, femtograms of original genomic target DNA. Screening of host-guest interactions of the surface attached DNA has found an interest among pharmaceutical and medical chemists as well as in environmental research. High sensitivity typical for the detection of DNA structural changes and damage is of great and unique importance in various fields.General trend to microfabrication concerns also recent development on this topic. For instance, miniaturized DNA chips were created, particularly regarding DNA hybridization. The DNA microarrays integrated in multiple biosensors should lead to the simultaneous analysis of samples with different analytes. Application of nanostructures has been shown as a way for significant enhancement of the sensitivity of the sensors. The development of single-use sensors based, for instance, on screen-printing technology is of practical interest for routine analysis.Further increase of interest to DNA based sensors can be expected in near future together with a commercial production of these devices and their wide use. However, basic research is still necessary to improve the sensor technologies, sensing strategies as well as analytical instrumentations and procedures. Papers collected in this special issue are from good known labs and represent the directions mentioned above. I would like to thank the contributors and I hope that the special issue of our Sensors will stimulate an interest to both the DNA based devices and the Journal.Prof. Dr. Jan LabudaThe Guest Editor © 2005 by MDPI ( http://www.mdpi.org). Reproduction is permitted for noncommercial purposes. Share and Cite MDPI and ACS Style Labuda, J. Special Issue Preface, DNA Based Sensors. Sensors 2005, 5, 343. https://doi.org/10.3390/s5060343 AMA Style Labuda J. Special Issue Preface, DNA Based Sensors. Sensors. 2005; 5(6):343. https://doi.org/10.3390/s5060343 Chicago/Turabian Style Labuda, Jan. 2005. "Special Issue Preface, DNA Based Sensors" Sensors 5, no. 6: 343. https://doi.org/10.3390/s5060343 Find Other Styles Article Metrics No No Article Access Statistics For more information on the journal statistics, click here. Multiple requests from the same IP address are counted as one view.

Session 6 Primary prevention of breast cancer II: Update of chemoprevention with tamoxifen, raloxifen and aromatase-inhibitors: S17. Aromatase inhibitors in breast cancer prevention: The IBIS-II trial

Medicinal/Pharmaceutical chemistry deals with the discovery, desin, development and both pharmacological and analytical characterisation of drug substances. Medicinal chemists are indispensible in the preclinical stages of drug development, and again as pharmaceutical chemists in drug quality control. The chapter describes stages of drug development (hit to lead to preclinical candidate to drug substance), followed by a summary of the phases of drug activity relating to a drug#s formulation, pharmacokinetics and pharmacodynamics. Finally, classification systems for marketed drug substances are presented, with an emphasis on the classification by molecular target.

CHALLENGES FOR MEDICINAL CHEMISTRY

THE DIRECTORS OF MEDICINAL chemistry and drug discovery from more than a dozen drug firms met with chemistry faculty from six universities at the newly opened Wyeth Research facility in Collegeville, Pa., earlier this month, as the American Chemical Society convened its first summit on the future of chemistry in pharmaceutical research. While all agreed that the future is secure, attendees at the ACS pharmaceuticals meeting, which was chaired by ACS President Eisa Reichmanis, raised concerns about medicinal chemistry being eclipsed by biological techniques in drug discovery. A drop in the number of bachelor's- and master's-degree level scientists entering the field was also a top concern, with discussion centering on improved cooperation between industry and academia in preparing students for careers as pharmaceutical chemists. Robert R. Ruffolo Jr., president of R&D at Wyeth, set the tone for an afternoon of open discussion in his welcoming address. Chemistry has always been the bread and butter of ...

Editorial1953 - 2003: 50thAnniversary of Planta Medica

On April 8, 2003 the Society of Medicinal Plant Research (Gesellschaft für Arzneipflanzenforschung) celebrated its 50th anniversary in Bad Camberg near Frankfurt, Germany. The founders of the Society were some German physicians who had experienced some disadvantages of modern medication and observed some healing effects of medicinal plants as well. Together with pharmacognosists, pharmaceutical chemists and industrial and approved pharmacists they set out to verify the effects of medicinal plants scientifically. The founding meeting on April 8, 1953 and the long journey of the Society to its position today is well described in the about 170 pages-long booklet ”Society for Medicinal Plant Research - 50 Years 1953 - 2003 - A Jubilee Edition” that was published this year by the Wissenschaftliche Verlagsgesellschaft Stuttgart (ISBN 3 - 8047 2028 - 5). During the founding meeting the idea of a scientific journal covering research on medicinal plants was further developed and as little as two months later, in June 1953, the first issue of the new journal Planta Medica appeared (Fig. [1]). The first editorial by Dr. Ernst Meyer, one of the founders, presented the goals and aims of the new journal: This first issue of the scientific journal Planta Medica is intended to become the focus and nucleus of crystallization for the entire scientific literature related to medicinal plant research. It is the goal to familiarize therapeutic practitioners with the application of plant-derived medicinal drugs and to enable medical doctors to enlarge their knowledge of the treasures of medicinal drugs according to the newest state of scientific research. Outstanding scientists chosen as editors from the membership of our Society guarantee a sound development of the journal in the fullest intention of the set goals.

WHEN PROCESS CHEMISTS MEET

PROCESS CHEMISTRY HAS BEEN described as the interface between organic chemistry and business: Pharmaceutical process chemists serve as the architects that make the connection between the two, building a bridge from drug discovery to large-scale production. The role of process chemists is to develop a safe and cost-effective process to prepare a drug substance that can ultimately be used for commercial production, commented Judith H. Cohen, a research scientist at Johnson & Johnson Pharmaceutical R&D in Spring House, Pa. Cohen spoke at the ACS Prospectives conference titled Process Chemistry in the Pharmaceutical Industry, held last month in San Juan, PR. Process chemists generally begin work on a new process by evaluating an existing synthetic method—usually provided by drug discovery—that may or may not be suitable for scale-up, she said. Our goal is to eliminate any hazardous reaction conditions, reagents, and solvents. We also have to look at the practicality of ...

Regulation of pancreatic beta-cell glucokinase: from basics to therapeutics.

Glucokinase (GK) serves as glucose sensor in pancreatic beta-cells and in other glucose sensor cells in the body. Biochemical genetic studies have characterized many activating and inactivating GK mutants that have been discovered in patients with hyperinsulinemic hypoglycemia or diabetes, all inherited as autosomal dominant traits. Mathematical modeling of the kinetic data of recombinant human wild-type and mutant GK accurately predicts the effects of GK mutations on the threshold of glucose-stimulated insulin release and glucose homeostasis. Structure/function studies of the enzyme suggest the existence of a hitherto unknown allosteric activator site of the enzyme that has significant implications for the physiological chemistry of GK-containing cells, particularly the pancreatic beta-cells. Glucose is the preeminent positive regulator of beta-cell GK expression and involves molecular mechanisms that are still to be elucidated in detail, but seem to have a specific requirement for increased glucose metabolism. Pharmaceutical chemists, motivated by the clear tenets of the GK glucose-sensor paradigm, have searched for and have discovered a novel class of GK activator molecules. The therapeutic application of this basic discovery offers a new principle for drug therapy of diabetes.

Estudio sobre automedicación en la Universidad de Antioquia, Medellín, Colombia

Se presenta una investigación exploratoria y descriptiva de corte transversal sobre la automedicación en la Universidad de Antioquia. Se plantea que diversas variables asociadas a los medicamentos pueden contribuir a problemas de salud pública por el uso no óptimo de los mismos. Se pretende dar a conocer a la comunidad universitaria cuál es su situación al respecto y obtener información preliminar para futuras investigaciones como base para formular estrategias que permitan incentivar la utilización sana de los medicamentos. Según diversos estudios, la cantidad de fármacos automedicados crece continuamente en el país y en el mundo. A este fenómeno parece no escaparse la Universidad de Antioquia. Este hábito tiene importantes repercusiones en la salud y en el rol del Químico Farmacéutico (QF) como integrante del sistema de salud. A pesar de que la comunidad universitaria conoce las implicaciones, riesgos y desventajas del uso inapropiado de medicamentos, se halló que el 97% de las personas se automedican, a pesar de que el 88% informan que conocen el posible riesgo de este hábito. También usan las medicinas alternativas aunque consultan con frecuencia al médico.

Beta-lactamase-mediated resistance and opportunities for its control.

Clinical use of beta-lactams has selected for beta-lactamase-producing organisms. Numerous beta-lactamases are known, and sequencing allows them to be divided into four Classes, A to D, with Classes A and C being the most important. Pharmaceutical chemists have responded to the spread of beta-lactamase-producing organisms by developing stable agents and inhibitors. Stability in penicillins and cephalosporins is achieved by attaching a bulky substituent to the amino group of 6-aminopenicillanic acid or 7-aminocephalosporanic acid, or by replacing the hydrogen on carbon 6 (penicillins) or 7 (cephalosporins) with an alpha-methoxy group. In carbapenems, stability is achieved by incorporation of a simple trans-6-hydroxyethyl group. Beta-lactamase-inhibitory activity occurs in many beta-lactam classes but only clavams and penicillanic acid sulphones have been developed specifically as beta-lactamase inhibitors. These inhibit most Class A and some Class D enzymes but act poorly against Class B and C enzymes. Their success is affected by the amount of enzyme, the permeability of the bacterial cell wall, the partner beta-lactam and the pH. Piperacillin/tazobactam, which combines a good inhibitor of Class A enzymes with a broad-spectrum, easily-protected penicillin, has wide activity against common pathogens, the major exceptions being strains of Enterobacter, Serratia and Citrobacter freundii that produce large amounts of Class C enzymes, and Gram-positive cocci with modified penicillin-binding proteins. Beta-lactamase-stable beta-lactams and inhibitor combinations overcome many existing resistance mechanisms but are themselves selecting new resistances. Few new beta-lactams able to overcome these resistances are advanced in development and consequently the opportunities for control lie mostly in the more prudent use of compounds already available.

The influence of extracts of Tricholomopsis rutilans (schff.ex fr.) sing. on the binding of LPS to CD14‐cells and on the release of inflammatory mediators

Looking for new pharmacologically active agents or lead structures, pharmaceutical chemists and biologists have traditionally dealt with secondary products from terrestrial plants and animals. During the past few years fungi have become more and more integrated into different screening systems. Antibacterial and immune response modifying compounds from fungi are known (Lindequist et al., 1990). Various basidiomycetes extracts were tested for their ability to inhibit the binding of lipopolysaccharide (endo-­toxin, LPS) to the endotoxin receptor CD14 and their influence on the release of mediators such as interleukin 1 (IL-1), interleukin 6 (IL-6) and tumour necrosis factor α (TNF-α). We tested the ethanol extracts of the whole fungi as well as extracts of the skin and the fruiting bodies and cultivated mycelium. The ethanol extracts of Tricholomopsis rutilans reduced the binding of LPS and the release of mediators. In a concentration of 100 μg/mL there was an inhibition by more than a half of the LPS binding. Furthermore we found a significant decrease in the LPS-induced release of IL-1 and TNF-α in a concentration dependent manner. The skin extract of T. rutilans was selected for further examination and isolation of active compounds. © 1998 John Wiley & Sons, Ltd.

Qualitative Analysis of Solid Phase Synthesis Reaction Products by X-ray Spectrometry

Abstract: A novel method for the synthesis of polypeptides using polystyrene/divinylbenzene copolymers as solid supports has drawn the attention of medicinal, pharmaceutical, and agricultural chemists because of its utility in combinatorial chemistry and parallel synthesis. In this method, arrays of solid-phase organic synthesis experiments are conducted simultaneously thereby enabling the preparation of large numbers of novel compounds over a short time period. The analysis of organic compounds attached to polymer supports presents unique challenges to chemists. This study presents some results of the application of energy-dispersive X-ray spectrometry (EDS) in the environmental scanning electron microscope (ESEM) to this problem. EDS in the ESEM has the advantages of minimal sample size, speed, and simplicity because the analyses are performed without special specimen preparation. The progress of a two-step synthetic transformation was followed using EDS-ESEM by the presence of a sulfur peak in the first synthetic step and by a bromine peak in the second step. The synthetic products were also evaluated by infrared spectroscopy and by elemental analysis (ion chromatography). The agreement of the qualitative analysis among all three techniques was good. Analysis by EDS-ESEM not only complements current analytical techniques in solid phase synthesis; it also provides insight into the details of the synthetic transformation.

Practice of ambulatory anesthesia in honduras: The central American experience

H ONDURAS IS A developing country, with scarcely 5 million inhabitants and 112,000 km 2 of territorial extension. The entire country has only 52 anesthesiologists, all of whom completed residency training abroad because it is not available in the educational programs of the local medical schools. What occurs is that the anesthe~ sia specialists train paramedical personnel to be anesthetic technicians who will be working at the public hospitals under the anesthesiologist's supervision. This allows them to meet the needs of the people in the field. Even though Honduras has not suffered the deleterious effects of war, it endures other problems, such as the two clearly separate socioeconomic poles of the miserable poverty (in the largest percentage) and the ostentatious richness, with a very small middle class. The world crisis is more visible in this type of society, which has generated excessive violence, thievery, and misery. Nevertheless, there are some advantages in this ongoing smuggle. Necessity is the mother of invention, and although anesthesiologists in Honduras do not have international fame, they have been obligated to improvise with materials and equipment in their dally practice (adhesive tape has become our number 1 auxiliary). The adoption of a saving policy to face the precarious situation has helped to overcome the necessities. The upper class might not be accustomed to these medical behaviors, but the resources must be well spent and waste avoided i f it is possible. New inventions from the medical engineering field have given us accurate devices to obtain better measurement, precise evaluation, and prompt treatment of the patient. The great activity of pharmaceutical laboratory chemists have launched many new products to the medicine market that make the practice of anesthesiology easier, safer, and more efficient. In developed countries this reality has made a real change because of the lower costs for medical care due to the ability to have patients hospitalized for a shorter period of time. It is economically attractive for the administration of hospitals or health care facilities to treat several patients per day with a short postoperative time rather than to have beds perpetually occupied. The profits are larger with the new methods. In Third World Countries, many things regarding medical service are done backwards (day surgeIaj is no exception) because of the difficulty to obtain expensive modern drugs and devices. There are arguments among the administrations because they would rather give affordable (or inexpensive) health care, believing this is the best solution to the crisis that the health care system faces, without making an effort to understand and compare the cost per day for inpatient care versus the technology investment and the acquisition of new drags that will allow a short hospital stay, which is what makes this kind of practice profitable. What occurs in private practice regarding this matter? Hospital permanency of the postsurgical patient is extended as much as possible because of the profits obtained by them; therefore, we believe that the ambulatory surgery programs are not attractive to these kinds of nonspecific day surgery centers. In the late i940s some ideas of day surgery programs took shape in Latin America, but it was not until 1970 that Honduras began those programs when some procedures were done in long-stay medical centers under ambulatory surgery criteria. In those early days the operations performed were mostly adenotonsillectomy, circumcision, inguinal herniorrhaphy, cystocele correction, hand surgery, and more, but percent-