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Biomedical subjects

L Garcia

Publications and source records attributed to L Garcia.

At least 55 records · Page 3Linked to original sources
PubMed1999

The clinical effectiveness of a dentifrice containing triclosan and a copolymer for controlling breath odor measured organoleptically twelve hours after toothbrushing.

The objective of this double-blind clinical study was to investigate the effectiveness of a dentifrice containing triclosan and a copolymer, Colgate Total Toothpaste, for controlling breath odor twelve hours after brushing the teeth compared to a placebo dentifrice which did not contain triclosan or a copolymer. Breath odor was evaluated by a panel of four expert judges using a nine-point hedonic scale. Following a baseline evaluation of breath odor, prospective study subjects who presented scores above the threshold value for unpleasant breath odor were stratified by score, and randomized into two treatment groups. Subjects were provided with a soft-bristled toothbrush, and brushed their teeth thoroughly in their regular and customary manner with their assigned dentifrice. Subjects refrained from dental hygiene, breath mints, or mouth rinses for the next twelve hours, after which they were once again evaluated for breath odor. Sixty-three (63) adult male and female subjects from the Mississauga, Ontario, Canada area participated in the study. At twelve hours after brushing their teeth, subjects in both dentifrice treatment groups presented mean breath odor scores which were statistically significantly lower than the mean scores observed at baseline. However, the difference between the mean twelve-hour breath odor scores differed significantly between the two dentifrices. The mean twelve-hour breath odor score for the Colgate Total Toothpaste group was 4.77, which is within the range of values corresponding to pleasant breath odor; the mean twelve-hour breath odor score for the placebo group was 6.05, which is above the value corresponding to unpleasant breath odor. Thus, the results of this double-blind clinical study support the conclusion that Colgate Total Toothpaste provides effective control of breath odor at twelve hours after brushing the teeth.

Adolescent↗
PubMed1999

Therapeutic Angiogenesis Using Endocardial Approach to Administration: Techniques and Results.

The availability of various angiogenic growth factors and gene therapy vectors, and the demonstration of their angiogenic potential in animal models of chronic myocardial ischemia, has propelled their investigation in clinical trials of therapeutic angiogenesis in patients with ischemic heart disease. Although most preclinical studies have employed methods of prolonged drug delivery and local therapy, the need for repeated administration and invasive access has limited the clinical usefulness of these delivery strategies. Intracoronary and intravenous delivery, with their potential widespread applicability, has fueled their use in most clinical trials of therapeutic angiogenesis; however, the significant systemic recirculation, limited myocardial retention, and potential for serious systemic adverse events are major limitations to their clinical use. Epicardial delivery using surgical access has been used in several clinical studies, but the need for surgical access and general anesthesia may limit the usefulness of this technique. The development of percutaneous endocardial delivery catheters using fluoroscopic guidance or Biosense NOGA (Biosense Laboratories, Haifa, Israel) electromagnetic three- dimensional navigation system has generated significant interest in the use of this delivery strategy in therapeutic myocardial angiogenesis studies. These strategies are being intensively investigated in preclinical studies with clinical studies soon to follow. We describe the limited experience with these drug delivery devices.

Journal Article↗
PubMed1999

Therapeutic Angiogenesis Using Basic Fibroblast Growth Factor and Vascular Endothelial Growth Factor Using Various Delivery Strategies.

Therapeutic angiogenesis is a novel technique that may provide a treatment strategy for ischemic heart diseasepatients who are not candidates for standard revascularization procedures. It works by promoting the growth of blood vessels provide new venues for blood flow. Basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF) are the most widely studied angiogenic agents. They have been shown to induce functionally significant angiogenesis in various animal models of chronic myocardial ischemia using various delivery strategies. Preclinical and clinical studies using these growth factors are reviewed with an emphasis on the different delivery strategies,including intracoronary and intravenous delivery; left atrial injections; intrapericardial administration; local intravascular and perivascular delivery; and intramyocardial delivery using single bolus delivery, repeated administration, gene therapy, and sustained delivery. Although intracoronary and intravenous delivery may be preferred for their ease of use and their applicability to a large patient population, systemic recirculation and lack of sustained tissue exposure to these therapeutic agents may limit the usefulness of this approach. Intrapericardial and intramyocardial administration, sustained local delivery, and second-generation gene therapy vectors may allow a safer and more sustained administration and may be preferable for clinical use. However, only well-designed randomized, double-blind placebo-controlled trials using outcome measures tailored to myocardial angiogenesis will determine the feasibility and effectiveness of this treatment modality.

Journal Article↗
PubMed1998

The conformation of purified Toxoplasma gondii SAG1 antigen, secreted from engineered Pichia pastoris, is adequate for serorecognition and cell proliferation.

A truncated form of SAG1, the immunodominant surface antigen of Toxoplasma gondii, has been produced in the methylotrophic yeast, Pichia pastoris. By construction, the recombinant protein lacks C-terminal residues 308-336 which, in native SAG1, encompass the glycosylphosphatidylinositol anchorage site. Secretion of anchor-less SAG1 proceeded via the yeast prepro alpha-mating factor signal peptide and yielded two immunoreactive protein species having apparent molecular masses of 31.5 and 34.5 kDa, respectively, and differing only by N-glycosylation of the single Asn-X-Ser site present in the molecule. Purification of the anchor-less SAG1 was achieved by a combination of ion-exchange and size-exclusion chromatographies. N-terminal amino acid sequencing of the products indicated the presence of additional residues glutamic acid--alanine at the N-terminal end of the products. Despite incomplete processing and unnatural glycosylation, anchor-less SAG1 proteins apparently adopted a suitable conformation recognized by monoclonal and human serum-derived antibodies, specific for the native SAG1. In addition, the recombinant anchor-less SAG1 proved competent for inducing proliferation, in vitro, of mononuclear cells from seropositive individuals. Finally, properly adjuvanted anchor-less SAG1 was able to induce protection of mice against a lethal challenge with T. gondii tachyzoites.

Amino Acid Sequence↗
PubMed1998

Advances in the treatment of patients with pancreatic cancer: improvement in symptoms and survival time. The San Antonio Drug Development Team.

Pancreatic cancer is a major cause of death from cancer in both men and women in the USA and Europe. The disease causes pain and has a significant impact on the performance status of the patient. In a randomized trial vs 5-fluorouracil, the novel nucleoside analogue gemcitabine (GEMZAR) has been shown to provide clinical benefit for patients (decreased pain and improved performance status) as well as to improve the time to tumour progression and survival for patients with the disease. There are also other new agents that are presented in this discussion, such as the multi-targeted antifolate MTA, capecitabine and the ONYX-015 adenovirus, which replicates in, and kills, only p53-abnormal cells, which have the potential to have an impact on this terrible disease.

Antimetabolites, Antineoplastic↗
PubMed1998

The origin and role of erythema after carbon dioxide laser resurfacing. A clinical and histological study.

BACKGROUND: Transient erythema, which can last up to 3 months after carbon dioxide (CO2) laser skin resurfacing, is a usual side effect with pulsed or rapidly scanned CO2 lasers. OBJECTIVE: We evaluated the cause of erythema in the clinical setting and by histology in order to determine if and how we may decrease it, or even eliminate it. METHODS: Ten patients who underwent resurfacing were recruited to this study. Skin punch biopsies were taken at 0, 7, 21, and 90 days and analyzed by light microscopy. RESULTS: Erythema was noticed from about day 8, when the crusting on the skin surface was exfoliated. It reached its maximum intensity after 14 days, and had disappeared by 60-90 days. Histology showed an early inflammatory response, with an immature neopithelium, and rich vascularization. The normal epidermis had returned by 90 days, and during this period there was reduced optical scattering and absorption in melanin. CONCLUSION: Although the erythema is an unwanted side effect in the patient's eyes, it is to be expected and thus represents the effects of a combination of epidermal immaturity, reduced melanin absorption of light, reduced dermal optical scattering, and increased blood flow secondary to the surgically induced inflammatory response.

Aged↗
PubMed1998

[Management of the mitochondrial encephalopathies].

INTRODUCTION: In the management of mitochondrial diseases, it is most important to know what mitochondrias are, how they function and the pattern of inheritance present on the different conditions affecting them. DEVELOPMENT: An overview of mitochondrial function, inheritance, clinical and biochemical classification is done, reviewing the different fatty acid oxidation, pyruvic metabolism and respiratory chain defects. Classification by age of onset is also done. Approach to diagnosis, clinical aspects, laboratory findings and available treatment is discussed. Some comments about the use of a neurometabolic database are discussed, where more than 150 conditions are described in detail. CONCLUSIONS: By using the search capabilities of the software, a search by age of onset, symptoms, signs and laboratory findings help in reaching the most probable diagnosis in a given child, with its recommended current management.

Child, Preschool↗
PubMed1997

Regulation of intracellular chloride concentration in rat lactotrophs: possible role of mitochondria.

Increasing evidence is accumulating for the involvement of chloride ions in the stimulus-secretion coupling of pituitary cells. We show that the mean intracellular chloride concentration [Cl-]i of rat lactotroph cells maintained in culture is high, close to 60 mM (59.4 mM), using the Cl- sensitive fluorescent probe 6-methoxy-N-(3-sulfopropyl) quinolinium (SPQ), coupled with whole-cell patch-clamp recordings. We demonstrate that this high level is correlated with the presence of mitochondrial stores of Cl- as shown by the release of Cl- in response to various metabolic inhibitors. We determine that CCP (50 microM) induces a mean [Cl-]i increase of 15.8+/-5.8 mM, using combined electrophysiology and microspectrofluorimetry methods. These data strongly suggest that cell metabolism, including the mitochondrial function, modulate [Cl-]i.

Animals↗
PubMed1997

Neutralizing antibody responses induced by varicella-zoster virus gE and gB glycoproteins following infection, reactivation or immunization.

The purpose of this study was to compare the antibody responses to varicella-zoster virus (VZV) gE and gB after natural VZV infection and after vaccination with live attenuated OKA vaccine in order to determine the relative importance of these proteins as components of a subunit vaccine. Anti-VZV antibody titers determined by IFA were of the same order of magnitude in sera from individuals with a history of varicella and in vaccinated children but higher in individuals given booster vaccination. The titers of anti-gE and anti-gB antibodies were measured by ELISA using recombinant gE or gB as capture antigen. From these experiments, it appears that the ratio of anti-gE to anti-gB antibody is highly variable from one individual to another but relatively stable over a long period of time for a particular individual, even after a zoster episode. Neutralizing antibodies directed against gE or gB were also measured by subtracting the neutralization titers obtained before and after depletion of the specific antibodies on immobilized recombinant gE, gB, or both. This showed that, with respect to neutralization, anti-gE and anti-gB are equally prevalent in vaccinated children and that anti-gE is generally, but not always, predominant over anti-gB in VZV-infected individuals. Finally, antibodies to these two glycoproteins appear to be predominant among the neutralizing antibodies directed to other VZV antigens.

Adult↗
PubMed1997

Modulation of voltage-dependent Ca2+ conductance by changing Cl- concentration in rat lactotrophs.

In pituitary cells, voltage-dependent Ca2+ channels play an important role in such physiological processes as exocytosis, secretion, the cell cycle, and proliferation. Thus mechanisms that modulate voltage-dependent Ca2+ channel activity participate indirectly in regulating intracellular Ca2+ concentration. We have shown a new modulating mechanism for voltage-dependent Ca2+ channels by demonstrating that Ca2+ influx is influenced by Cl-. To evaluate the role of Cl- on Ca2+ conductance coupling, we first measured the intracellular Cl- concentration of rat lactotrophs using the Cl(-)-sensitive fluorescence probe sulfopropylquinolinium by simple microspectrofluorometry or combined with electrophysiology. We found an average intracellular Cl- concentration of rat lactotrophs of approximately 60 mM (n = 39). Using the whole cell tight-seal recording technique, we showed that a reduction in external Cl- concentration ([Cl-]o) and a decrease in Cl- conductances affected Ca2+ conductance as measured by Ba2+ movement through the Ca2+ channels (I(Ba)). Low [Cl-]o (39 mM) induced a decrease in Ca2+ entry via voltage-gated Ca2+ channels (-27.75 +/- 4% of normalized I(Ba)). Similarly, blockade of the Cl- conductance by 1 mM 9-anthracene carboxylic acid induced a decrease in I(Ba) (-26 +/- 6% of normalized I(Ba)). This modulation of I(Ba) was inhibited by 24-h pretreatment of the cells with pertussis toxin (1 microg/ml), suggesting that changes in Cl- concentration induced by low [Cl-]o and 9-anthracene carboxylic acid interfered with the phosphorylation of G proteins involved in Ca2+ channel activation. These results suggest a feedback mechanism based on constant interaction between Ca2+ and Cl-. Finally, they also emphasize the physiological role of Cl- in rat lactotrophs.

Animals↗
PubMed1997

Regulation of intracellular pH in rat lactotrophs: involvement of anionic exchangers.

Regulation of the intracellular pH (pHi) of normal rat lactotrophs was studied. As this cell type, cultured with 10% FCS, can achieve a relatively alkaline pHi (7.3-7.5), we investigated the presence of a mechanism based on Cl-/HCO3- exchange. Using the pHi-sensitive probe SNARF-1 (seminaphtorodafluor) in its permeant form, SNARF-1/AM, we studied pHi recovery after acidic loading in individual cells with a microspectrofluorometric approach. We showed the involvement of anionic exchange in lactotroph cell pHi regulation. Acute CO2-bicarbonate cell acidic loading combined with external Cl- depletion induces the activation of a Cl-/HCO3- exchange. This exchange is 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid sensitive and corresponds to the type 3 anionic exchanger (AE3). However, after nigericin acidification, Na+/H+ exchange can also participate in recovery. In addition, incubation experiments strongly suggest that a 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid-insensitive anionic exchanger (type 2 anionic exchanger or AE2) is present in rat lactotrophs. The presence and involvement of carbonic anhydrase in pHi regulation have been demonstrated. Finally, using Northern blot and reverse transcription-PCR techniques, messenger RNAs for both AE2 and AE3 were identified in anterior pituitary cell extracts. We concluded that in normal rat lactotrophs, pHi regulation is achieved by a complex system in which Cl-/HCO3- exchange has a pivotal role.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗
PubMed1996

Characterization of novel peptoid agonists for the CCK-A receptor.

The successful design of peptoid CCK-B receptor antagonists using rational approaches suggested that it might be feasible to develop similar non-peptide small molecule agonists with potential therapeutic applications. We now report the characterization of such a compound with full agonist activity at CCK-A receptors on rat exocrine pancreatic acinar cells. The compound, PD149164, stimulated a similar maximal response to CCK8 from the exocrine pancreas in anaesthetized rats in vivo, and from isolated pancreatic acini in vitro it also generated intracellular Ca2+ oscillations similar to those evoked by CCK8. These effects were inhibited by the CCK-A antagonist L-364,718. Interestingly, the enantiomer of PD149164, PD151932, was a CCK-A antagonist and blocked PD149164 stimulated effects on the exocrine pancreas. The data indicate that it is possible to develop both agonist and antagonist activities in enantiomers of small non-peptide molecules.

Adamantane↗
PubMed1996

Involvement of the dihydropyridine receptor and internal Ca2+ stores in myoblast fusion.

The process of myoblast fusion during skeletal myogenesis is calcium regulated. Both dihydropyridine receptor and ryanodine receptor are already present on muscle precursors, at the prefusional stage, before they are required for excitation-contraction coupling. Previous pharmacological studies have shown the need for a special pool of Ca2+ associated with the membrane for the fusion process to occur. We hypothesized that this pool of Ca2+ is mobilized via a machinery similar to that involved in excitation-contraction coupling. The process of fusion in rat L6 muscle precursors was either totally or partially abolished in the presence of the L-type calcium channel inhibitors SR33557 and nifedipine (half inhibition towards 2 microM), respectively. The inhibition was reversible and dose-dependent. Drugs able to deplete internal calcium stores (caffeine, ryanodine, and thapsigargin) were also tested on the fusion. Both caffeine and thapsigargin drastically inhibited fusion whereas ryanodine had no effect. This suggests that fusion may be controlled by internal pools of Ca2+ but that its regulation may be insensitive to ryanodine. We presumed that an early form of the ryanodine receptor may exist, with different pharmacological properties than the adult forms. Indeed, Western blot analysis of pre- and postfusional L6 cells demonstrated the presence, at the prefusional stage, of a transient form of the ryanodine receptor protein with an apparent molecular weight slightly different from those of the classical skeletal and cardiac forms. Taken together, these results support the hypothesis that the fusion process is driven by a mechanism involving both the dihydropyridine receptor (alpha1 subunit of the L-type Ca2+ channel) and the internal stores of Ca2+. The machinery underlying this mechanism might consist of slightly different forms of the classic molecules that in adult muscle ensure excitation-contraction coupling. It remains to be seen, however, whether the mobilization of the internal pool of Ca2+ is triggered by the type of mechanism already described in skeletal muscle.

Animals↗
PubMed1996

Pericardial effusion. Unusual complication in thyroid cancer.

A case in which a prolonged hypothyroid state resulted in development of a pericardial effusion is presented. The compensatory mechanism for protein homeostasis is lost in severe hypothyroidism. Iodine is transported to the pericardial space, which is filled with a high-protein content fluid and remains trapped. The mechanism for the accumulation of the fluid in the pericardial space is discussed. To prevent this unusual but dangerous complication, the authors recommend close monitoring of the patient's clinical status and serum thyroid stimulating hormone. The use of a short acting thyroxine substitute for at least 2 weeks can decrease occurrence of this complication and will shorten the time the patient needs to be hypothyroid.

Adult↗