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Biomedical subjects

P Maffei

Publications and source records attributed to P Maffei.

33 records · Page 2Linked to original sources
PubMed1999

Morphologic study of microcirculation in acromegaly by capillaroscopy.

Although wide range investigations on the heart and great vessels have been reported in acromegaly, the field of microcirculation is still largely vacant. The nailfold is a window through which we can observe in vivo the vascular bed. This study investigates through nailfold capillaroscopy the morphology of cutaneous microcirculation in acromegaly in relationship with the usual hormonal parameters of disease activity. Twenty-five acromegalic patients and 26 normal subjects, age and sex matched, were studied. A subgroup of acromegalics (8 patients) was considered in stable remission, and the remaining 17 had active disease. Capillaroscopy was performed in each subject by in vivo computer aided stereomicroscopy (magnification, x400). The following morphological parameters were calculated: the number of tortuous loops, meandering capillaries, and capillaries per millimeter; avascular areas; visibility of subpapillary plexus; the capillary length; and intercapillary distance. We were unable to perform the exam in 4 of 25 patients because visibility was poor. The capillary number and length were significantly reduced in acromegalics compared to controls [8.9 +/- 1.5 vs. 10.3 +/- 1.2 no./mm (P = 0.0010) and 174 +/- 49 vs. 255 +/- 24 microm (P < 0.0001)]. Moreover, in acromegalics, the numbers of tortuous loops and meandering capillaries were significantly increased [19 +/- 8 vs. 13 +/- 5 (P = 0.0027) and 10 +/- 12 vs. 0.7 +/- 1.1 (P < 0.0001)]. The capillaroscopic alterations were still observed in a smaller group of 8 nondiabetic and nonhypertensive acromegalics. We found branch-like capillaries in 4 acromegalic patients, but not in the control group. Finally, we observed a meaningful different and ameliorated capillaroscopic morphology in acromegalic patients in stable remission compared to active disease patients as far as the total number (density) and meandering capillaries were concerned. In conclusion, our study shows that in acromegaly, morphological alterations also affect the peripheral microcirculation, which seems to be influenced by the activity of the disease. We believe that nailfold capillaroscopy may represent an additional useful tool in the follow-up of acromegalic patients.

Acromegaly↗
PubMed1997

Association study of schizophrenia and the histidase gene.

Previous findings of increased heterozygosity for histidinemia among schizophrenic patients make the histidase gene a plausible candidate for genetic studies in schizophrenia. In the present study, we used a tetranucleotide repeat polymorphism in intron 8 of the histidase gene to examine the possibility that the histidase gene contributes to the genetic component of schizophrenia. In a first sample of 161 patients and 128 controls, we found the 4 repeat allele to be in excess in the patients. In contrast, the 3 repeat allele was less frequent in patients. A second sample of 95 patients and 93 controls was utilized to test these hypotheses. However, both observations were not replicated. We therefore concluded that our results do not support an involvement of the histidase gene in the development of schizophrenia.

Alleles↗
PubMed1995

Gender-dependent variability of signal-averaged electrocardiogram in acromegaly.

Ventricular late potentials are obtained by signal-averaged surface electrocardiography. Late potentials in normal subjects may be influenced by physiological elements such as gender, height and body mass index. Considering that growth hormone (GH) hypersecretion is able to markedly alter different anthropometric variables, we studied the relation between these elements and the late potentials of 22 acromegalic patients. Males registered higher absolute QRS duration and LAS40 (low-amplitude signal) and, on the opposite, lower RMS40 (root mean square) in comparison to females; QRS duration and LAS40 seem to depend, however, on the different anthropometric variables, since their normalization with height and lean body mass (LBM) abolishes gender-dependent differences. On the contrary, the persistence, among males, of lower RMS40 in respect to females even after normalization for height, LBM and insulin-like growth factor 1 values makes it likely that the latter ECG variable is independent of the anthropometric ones and from the disease's activity. Moreover, males appear to be more vulnerable to GH heart-harming activity.

Acromegaly↗
PubMedDate not supplied

Design and evaluation of buccal adhesive hydrocortisone acetate (HCA) tablets.

Many studies have shown that topical buccal therapy with steroid anti-inflammatory drugs is useful in controlling ulcerative and inflammatory mucosal diseases. This local treatment is based on the concept that a high activity of steroids can be produced at the site of administration and, at the same time, the degree of systemic side effects can be minimized or avoided. In this study we developed a new formulation consisting of a mucoadhesive tablet formulation for buccal administration of hydrocortisone acetate (HCA). Three types of tablet were developed containing three mucoadhesive components: hydroxypropylmethyl cellulose (Methocel K4M), carboxyvinyl polymer (Carbopol 974P), and polycarbophyl (Noveon AA1); the first polymer is a cellulose derivative, the others are both polyacrylic acid derivatives. For each of those, three tablet batches were produced changing the quantity of the mucoadhesive component (10, 20, and 30%), resulting in 9 different formulations. The compatibility of HCA with all excipients using Differential Scanning Calorimetry (DSC) was assessed. Tablets were manufactured by wet granulation followed by compression. Technological controls on granulates (Hausner index, Carr index, granulometry and Karl-Fischer percentage humidity) and tablets (thickness, diameter, friability, hardness, uniformity of content, weigh uniformity and dissolution kinetic) were carried out. Mucoadhesion properties, ex vivo permeability through porcine buccal mucosa, in vivo behavior and compliance were evaluated. Technological controls have demonstrated that the increase in the (percentage) of mucoadhesive causes an increase in granulometry followed by a reduction in the granulate flowability, however all the tablets have given satisfactory technological results and conformed to the 3rd Ed. European Pharmacopoeia specifications. Mucoadhesion, ex vivo permeability and in vivo behavior results notably differed among tablets, depending on the quality and quantity of the mucoadhesive component. An overall comparison of results showed the tablets containing Carbopol 20% resulted to be the best formulation among those developed.

Acrylates↗
PubMedDate not supplied

In vitro permeation screening of a new formulation of thiocolchicoside containing various enhancers.

Thiocolchicoside, a muscle relaxant agent with anti-inflammatory and analgesic actions, also is used topically for the treatment of muscular spasms and for rheumatologic, orthopedic, and traumatologic disorders. In this study, thiocolchicoside was formulated to use as foam to avoid contact with the afflicted area during the spreading phase. To enhance drug penetration, various enhancers were added to the base formulation. The tested enhancers were ethoxyethylendiglycol (Transcutol), highly purified phosphatidylcholine (Lipoid S20), capsaicin, propylene glycol dipelargonate (DPPG), and glycolysed ethoxylated glycerides (Labrafil M1944 CS). The transdermal absorption of the tested formulations containing enhancers, in comparison with base formulation, was evaluated in vitro through rat skin using standard Franz diffusion cells. Base formulation was found to have a higher permeation profile than the simple aqueous and hydroalcoholic solutions of the drug, meaning that the base formulation by itself enhances the drug permeation. Among the tested formulations, only the formulation containing DPPG/ethanol was found to be statistically different, showing an enhancement factor of 3.58. In the same experimental session, Muscoril ointment, the commercially available pharmaceutical product containing the same thiocolchicoside concentration (0.25%), also was tested. The formulation containing DPPG/ethanol showed a 4.86 times increase of permeability constant in comparison with Muscoril ointment. The formulation containing DPPG/ethanol as an enhancer could be a good candidate for a new topical foam, considering its good characteristics of permeability and compliance.

Administration, Cutaneous↗
PubMedDate not supplied

Correlation between the transdermal permeation of ketoprofen and its solubility in mixtures of a pH 6.5 phosphate buffer and various solvents.

The passage of a drug through the skin is directly proportional to the concentration of the drug in the donor phase and to the permeability coefficient constant Kp. Kp is determined essentially by two factors: the dissolution of the drug in the stratum corneum (measured by the partition coefficient P) and the diffusion in the same stratum (measured by the diffusion constant D). In our study, several saturated solutions of ketoprofen in mixtures of a pH 6.5 phosphate buffer and various co-solvents were studied to find correlations between the solubility of the ketoprofen in the mixtures and its permeation parameters in in vitro permeation studies with Franz cells. The results show that D does not change in the different mixtures; the diffusion of the drug into the stratum corneum is not influenced by the presence of the co-solvents, whereas the partition coefficient is strongly influenced. In particular, Kp and P were found to be inversely proportional to solubility, meaning that when the co-solvent increases the solubility, the partition of the drug and consequently Kp decrease. These findings were confirmed in some developed gels, and the developed gels were found to enhance the ketoprofen permeation with respect to the formulation in a commercial Fastum gel.

Administration, Cutaneous↗
PubMedDate not supplied

Mucoadhesive tablets for buccal administration containing sodium nimesulide.

The possibility of improving the flux of nimesulide across the buccal mucosa using the drug in the form of a sodium salt was investigated in our study. The salt form may increase to flux across buccal membrane, starting from a suspension; its lower permeation coefficient is compensated by a higher concentration gradient. The salt was inserted into a mucoadhesive tablet for buccal administration. The tablets were designed to prevent the loss of the drug into the saliva by means of a protective layer and placed on the area not in contact with the mucosa. Ten volunteers were used. The in vitro release from mucoadhesive tablets was examined through a porcine buccal mucosa, using a standard Franz cell, modified for present purposes. The advantages of a higher concentration gradient for the flux, related to a higher solubility of the salt, and to a sufficiently high permeation coefficient of the drug, despite the ionized form, could not be completely exploited, because the composition of the formulation destroys the chemical form of the drug.

Adhesives↗