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Biomedical subjects

M Gramiccia

Publications and source records attributed to M Gramiccia.

At least 55 records · Page 3Linked to original sources
PubMed1992

Decreased sensitivity to meglumine antimoniate (Glucantime) of Leishmania infantum isolated from dogs after several courses of drug treatment.

Although unresponsiveness to antimonial drugs in human leishmaniasis appears to be increasing, resistance to antimony in Leishmania is not well documented. Treatment of leishmaniasis in dogs, the domestic reservoir of L. infantum, with meglumine antimoniate (Glucantime) is a common practice in many Mediterranean countries. The dogs, however, remain highly infective to the phlebotomine vectors, even after several courses of treatment. A study was therefore carried out to test the comparative susceptibility to meglumine antimoniate of L. infantum stocks isolated from four naturally-infected dogs, before (BT) and after treatment (AT) with three to six courses of the drug, and used to infect Balb/c mice. Significant differences in suppression between the BT and AT stocks were observed in the infected mice when they were given the drug at a rate of 0.01-10 mg kg-1 day-1 for five days. Each AT stock was between eight and 41 times more resistant to meglumine antimoniate than the BT stock from the same dog, in terms of the ratios of the AT ED50 values to the corresponding BT values, which were calculated as indices of resistance. This result underlines the futility and danger of repeated antimonial treatments of dogs with signs of leishmaniasis, as these may produce a permanent reservoir of parasites unsusceptible to the drugs in human clinical use.

Animals↗
PubMed1991

The amino aldehydes produced by spermine and spermidine oxidation with maize polyamine oxidase have anti-leishmanial effect.

Purified maize polyamine oxidase bound to hydroxylapatite was utilized as an enzymatic reactor to produce oxidized spermidine and spermine. The oxidation products showed a consistent inhibitory activity on Leishmania infantum in mice. 1,3-diaminopropane showed a much lower activity. Moreover chemically prepared 4-aminobutyraldehyde had a similar ED50 to that of oxidized spermidine. It is concluded that among the compounds arising from polyamine oxidation those with the greatest anti-leishmanial effect are 4-aminobutyraldehyde and 1-(3-aminopropyl)-4-aminobutyraldehyde.

Aldehydes↗
PubMed1991

Synthesis and antileishmanial activity of some 1- or 2-(dihydroxyalkyl) and 3-(dihydroxyalkoxy)pyrazolo [3,4-d] pyrimidines.

Several new derivatives of 4-amino-, 4,6-diamino- and 4-hydrazino-[3,4-d]pyrimidine dihydroxyalkyl substituted in the 1 or 2 positions, or dihydroxyalkoxy substituted in the 3 position have been synthesized. Some of these compounds were evaluated for their activity against Leishmania infantum in mice. The highest degree of antileishmanial activity was displayed by the 4-amino-1-(dihydroxyalkyl) derivatives which yielded parasite inhibition values nearly comparable with that of glucantime in a standard 5-day test.

Animals↗
PubMed1990

Leishmaniasis in Sardinia. IV. Epidemiological appraisal of cutaneous leishmaniasis and biochemical characterization of isolates.

Cutaneous leishmaniasis (CL) is endemic in Sardinia where 250 cases were reported from 1922 to 1988. The province of Sassari, in the north of the island, shows the highest number of cases. The vertical distribution of localities where cases had occurred is analysed and the age distribution of cases is given. Isolation of parasites was attempted in 12 cases, but successful growth of Leishmania was obtained from three cultures only. The stocks belonged to two different zymodemes of L. infantum: zymodeme Montpellier (ZMON) 24 and ZMON 24 MPI variant. The distribution of dermotropic L. infantum zymodemes in the Mediterranean area is discussed and the presence of a possible parasite reservoir is suggested.

Age Factors↗
PubMed1989

A kinetoplast DNA probe diagnostic for Leishmania major: sequence homologies between regions of Leishmania minicircles.

A restriction fragment from a cloned kinetoplast minicircle DNA has been shown to be diagnostic for Leishmania major. This 402-bp TaqI fragment has been used routinely (as a radiolabelled probe) to detect 10(4) parasites in simple dot blots, both experimentally and in epidemiological surveys. It positively identified all stocks of L. major tested (including all six known zymodemes) and showed very low homology to kinetoplast DNA (kDNA) and chromosomal DNA of Leishmania infantum and Leishmania tropica, two species commonly isolated from patients and wild hosts within foci of L. major in the Old World. DNA sequence analysis of a minicircle of L. major is reported for the first time, and it is demonstrated that this species shares with Leishmania aethiopica, Sauroleishmania tarentolae and several species of Trypanosoma a region of conserved sequence that is involved in DNA replication, a process that could present targets for selective chemotherapeutic attack. Sequence and restriction fragment analyses have indicated the difficulties of selecting species-specific sequences from kDNA which, even in the same parasite clone, contains several predominant minicircle classes, not all of which contain diagnostic sequences.

Animals↗
PubMed1989

Study on genetic polymorphism of Leishmania infantum through the analysis of restriction enzyme digestion patterns of kinetoplast DNA.

Twenty-nine Leishmania infantum strains characterized by different host source, tropism and belonging to 6 zymodemes, were examined by restriction enzyme analysis of kinetoplast DNA (kDNA) using 15 endonucleases. The enzymes which produced only one fragment revealed full identity between all the strains examined, while those producing many bands gave different electrophoretic patterns. They were interpreted with the aid of numerical analyses (cluster and multifactorial analysis). The results show a cline of genetic variability among the strains, the highest similarity being observed between most of the viscerotropic strains isolated from man, dog, black rat and sandflies. The strain agents of human cutaneous leishmaniasis show a varying degree of genetic divergence from this group, which appears more evident when characters from isoenzymes are considered.

Animals↗
PubMed1989

In vivo effect of eflornithine (DFMO) and some related compounds on Leishmania infantum preliminary communication.

An in vivo method was used to test the effect of eflornithine (DFMO) and five related compounds on Leishmania infantum amastigotes. Treatment with 100 mg/kg sc for 5 days of Leishmania infected Balb/c mice yielded a parasite inhibition ranging from 56% (compound 2, "reverse arginine") to 85% (eflornithine), these values being lower than that obtained with the reference compound Glucantime (93%). In long-term treatment (40 days) the two selected compounds, eflornithine and 3 ("reverse homoarginine"), failed to cure the animals. However, in dose response experiments these drugs showed to be effective at very low doses when compared with Glucantime, thus suggesting that they might be of potential value in the chemotherapy of leishmaniases.

Animals↗
PubMed1988

Natural infections of phlebotomine sandflies with Trypanosomatidae in central and south Italy.

In a survey of Leishmania infections of phlebotomine sandflies caught in central and south Italy in 1986, zymodeme MON-1 (Montpellier 1) of Leishmania infantum was isolated from Phlebotomus perniciosus and L. tarentolae [= Trypanosoma platydactyli?] was isolated from Sergentomyia minuta, providing for mainland Italy the first direct proof of these long-suspected parasite-vector associations. The roles of P. perfiliewi and P. perniciosus in the transmission of Leishmania spp. in Italy are discussed.

Animals↗
PubMed1988

Studies on canine leishmaniasis control. 1. Evolution of infection of different clinical forms of canine leishmaniasis following antimonial treatment.

81 dogs naturally infected with Leishmania infantum in the Isle of Elba, Italy, were treated with meglumine antimoniate (Glucantime). 36 of them (45.5%) were asymptomatic cases. 4-24 months after treatment the dogs were clinically and serologically examined; the recovery rates were 47.2% for asymptomatic cases, 33.3% for oligosymptomatic cases, and 11.1% for symptomatic cases. Furthermore, treatment had prevented the development of patent disease in 90% of non-recovered asymptomatic cases, whereas it had produced only slight improvement of clinical condition in patent dogs which were still infected after drug administration. Treatment with antimonial drugs is therefore recommended in canine leishmaniasis control if non-patent or sub-clinical forms of the disease are detected by seroepidemiological surveys.

Animals↗
PubMed1988

Studies on canine leishmaniasis control. 2. Effectiveness of control measures against canine leishmaniasis in the Isle of Elba, Italy.

A serological and parasitological survey carried out in 1985 in the Isle of Elba, Italy, revealed a high prevalence of canine leishmaniasis. This focus was considered ideal for the evaluation of effectiveness of treating infected dogs with meglumine antimoniate, applied as a control measure during 1985 and 1986. New data on prevalence were obtained for the years 1986 and 1987. Incidence of new canine leishmaniasis cases after the transmission seasons 1984, 1985 and 1986 were determined by examining 2 cohorts: cohort I, dogs born within 2 transmission seasons, and cohort II, adult dogs examined and found to be negative before each transmission season. Over 2000 tests were carried out on 1500 dogs. Prevalence analysis showed a reduction of infective dogs (symptomatic and oligosymptomatic) from 14.4% in 1985 to 5.2% in 1987. Incidence analysis showed a decrease of new cases from 12.4% after transmission season 1984 to 4.6% after transmission season 1987. The results indicate a two-thirds reduction of the disease frequency in dogs of the Isle of Elba after a 2-year period of control measures.

Animals↗
PubMed1987

Leishmania infantum sensu lato as an agent of cutaneous leishmaniasis in Abruzzi region (Italy).

The extreme difficulty of culturing in vitro parasites from Italian causes of cutaneous leishmaniasis (CL) has so far been a handicap to their biochemical identification. A technique based on the "transient growth" of promastigotes originating from parasites visceralized in LHC inbred hamsters was used. Through this technique, promastigote extracts of seven Leishmania isolates from CL cases from the Abruzzi region were obtained. Isoenzyme profiles of these isolates and reference strains of L. tropica, L. major and L. infantum were compared using 11 enzymes (ASAT, PGM, GPI, 6PGD, G6PD, ME, MDH, MPI, IDH, NH1 and NH2). Six isolates differed from L. infantum in one enzyme only (NH1), and one isolate was indistinguishable from L. infantum for all enzymes tested.

Humans↗
PubMed1987

Natural infection of Phlebotomus perfiliewi with Leishmania infantum in a cutaneous leishmaniasis focus of the Abruzzi region, Italy.

One out of 213 Phlebotomus perfiliewi caught from an endemic cutaneous leishmaniasis focus in Abruzzi region (Italy) was naturally infected with promastigotes. The parasites were grown in culture medium and in a hamster, typed by the examination of 11 isoenzymes, and found to be indistinguishable from Leishmania infantum s.st. (Montpellier zymodeme 1). The probable role of P. perfiliewi in the transmission of cutaneous leishmaniasis due to L. infantum s.l. in the focus is discussed.

Animals↗
PubMed1987

Leishmania infantum infection rates in Phlebotomus perniciosus fed on naturally infected dogs under antimonial treatment.

Dogs naturally infected with Leishmania infantum Nicolle were treated with three courses of meglumine antimoniate. Changes were observed in the dogs' clinical signs, antibody titres and in infection rates of Phlebotomus perniciosus Newstead fed on the dogs. A large reduction in the sandfly infection rate was observed for 4-5 months after the first treatment. The use of antimonial drugs is advocated for the control of canine leishmaniasis and to reduce risks of L.infantum transmission.

Animals↗