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G Lorenzi

Publications and source records attributed to G Lorenzi.

At least 19 recordsLinked to original sources
PubMed1996

Special considerations concerning regulatory requirements and drug development for peptides and biotech products in the EU.

The marketing authorization for a new medicinal product is based on the scientific assessment of its quality, safety and efficacy. The marketing authorization application (MAA) which covers all the relevant documentation can be filed in the EU via different application procedures. For peptides and biological products special issues have to be taken into consideration during drug development. Due to special production procedures and the complexity of the active substance itself, peptides and biotech products are subject to specific regulatory requirements. This leads to the necessity to discuss the development program of a new peptide or biotech product with the health authorities on a case by case basis. This article will focus on the special regulatory requirements for peptides and biotech products including the registration procedures as well as technical, preclinical and clinical issues.

Biotechnology↗
PubMed1994

Development of a miniature bioreactor for continuous culture in a space laboratory.

A new type of miniature bioreactor for continuous culture of yeast cells in space laboratories has been developed. Silicon microtechnology has permitted the integration of numerous functions and systems in a volume of 87 x 63 x 63 mm3 and a weight of 610 g. The 100 ml of fresh medium can be delivered at variable flow rates to the cultivation chamber (volume 3 ml) by means of a micropump. The culture is agitated by a magnetic stirrer. Microsensors monitor pH, temperature and redox potential. The decrease of pH occurring during the cultivation of Saccharomyces cerevisiae is compensated electrochemically. A window allows the inspection of the culture status. Samples of up to 1 ml can be drawn through a silicone rubber septum. The data measured by the sensors are transmitted on-line to the ground station during operations in space. The bioreactor had to fulfil several requirements related to the safety regulation of the space agencies. In particular, new materials had to be selected and tested for their biocompatibility. The instrument has now passed all space and biological qualification tests and will be used in an experiment selected by ESA for the International Microgravity Laboratory-2 Mission in Spacelab in July 1994. This paper gives the results of the functional and biological tests and a detailed description of the instrument.

Fermentation↗
PubMed1994

Role of bypass, endarterectomy, extra-anatomic bypass and endovascular surgery in unilateral iliac occlusive disease: a review of 1257 cases.

Some 1257 patients who had undergone revascularization procedures for unilateral iliac occlusions were reviewed retrospectively. A total of 824 patients were operated upon using conventional operations, 165 patients had femorofemoral bypass and 268 were treated using endovascular surgery techniques. Revascularization was performed through an extraperitoneal approach by means of iliac thromboendarterectomy (560) or iliac femoral bypass (264) if there was a total occlusion of either the common or external iliac artery (group 1). A femorofemoral crossover bypass was inserted when the operative risk was considered to be high (group 2). Endovascular procedures (percutaneous transluminal angioplasty 234, laser percutaneous transluminal angioplasty 11, stenting 22, atherectomy one) were used in recent years to treat stenoses or occlusions of 3 cm or less (group 3). The indications for operation were severe claudication in 79.7% in group 1 and 92.6% in group 3, whereas in group 2 66.7% of patients presented with symptoms of more advanced ischaemia. The immediate patency rate was 97.0% after extraperitoneal reconstructive surgery, 96.9% in the femorofemoral group and 92.1% in patients having an endovascular procedure. The operative mortality rate was 0.7, 4.2, and 0.3% for groups 1-3, respectively. The 5-year patency rate, analysed by the life-table method, was 77.9% in group 1, 75.3% in group 2 and 73.7% in group 3 (P = n.s., log rank test). The different revascularization techniques were chosen on the basis of the type of disease present and the patient's general condition. All procedures appeared to be effective when correctly selected.

Adult↗
PubMed1993

Cultivation of hamster kidney cells in a dynamic cell culture system in space (Spacelab IML-1 Mission).

Cell proliferation, tissue plasminogen activator (t-PA) production and metabolic changes of Hamster Kidney cells (HaK) grown on microcarriers in an automatic Dynamic Cell Culture System (DCCS) were determined on the first International Microgravity Mission (IML-1) Spacelab (22-30 January 1992). The DCCS was designed for two cell culture chambers (volume: 200 microliters each), one operating as a hatch system, the other as a perfusion system. Medium exchange was achieved with an osmotic pump (flow rate 1 microliter h-1). Two major items were investigated: the biological performance of the DCCS in space and the effect of microgravity on HaK cells. The results obtained demonstrated that (1) the DCCS can be used for biological experiments on long term Spacelab missions. In fact, higher cell densities and higher concentration of glucose but lower concentration of lactate in the perfusion chambers than in the batch chambers were measured. The concentration of t-PA, glutamine and ammonia was similar in all chambers. (2) Microgravity had no effect on cell growth and metabolism of HaK cells.

Ammonia↗
PubMed1990

Actin filaments responsible for the location of the nucleus in the lentil statocyte are sensitive to gravity.

The location of the nucleus in statocytes or lentil roots grown: 1), at 1 g on the ground, 2), on a 1 g centrifuge in space, 3), in simulated microgravity on a slowly rotating clinostat (0.9 rmp) 4), in microgravity in space was investigated and statistically evaluated. In cells differentiated at 1 g on the ground, the nuclear membrane was almost in contact with the plasmalemma lining the proximal cell wall, whereas in statocytes of roots crown on the clinostat there was a distance of 0.47 micrometers (horizontal clinorotation) and or 0.76 micrometers (vertical clinorotation) between these membranes. However, in microgravity the nucleus was the most displaced, 0.87 micrometers from the proximal cell wall. Centrifugation of vertically grown roots in the root-tip direction showed that the threshold of centrifugal force to detach all nuclei from the proximal cell wall was about 40 g. In statocytes developed in the presence of cytochalasin B at 1 g the nuclei were sedimented on the amyloplasts at the distal cell pole, demonstrating that the location of the nucleus depends on actin filaments. The results obtained are in agreement with the hypothesis that gravity causes a tension of actin filaments and that this part of the cytoskeleton undergoes a relaxation in microgravity.

Actins↗
PubMed1990

Basal cell carcinoma arising in pemphigus vulgaris of the lower eyelid.

A 59-year-old woman on continuous treatment with corticosteroids and immunosuppressive drugs for pemphigus vulgaris of 14 year's duration presented with an enlarging nodular lesion on the right lower eyelid. The neoplasm, diagnosed as basal cell carcinoma, was excised conserving the lid margin, and eyelid reconstruction was done with a rotated cheek flap. Wound healing proceeded without complications in spite of immunosuppressive treatment, and the final cosmetic and functional result was satisfactory.

Basal Cell Carcinoma↗
PubMed1988

Gravitational effects on mammalian cells.

In this paper we present first the results of our most recent investigations on gravitational effects on the activation of human lymphocytes: by immunoenzymatic staining and by using concanavalin A (Con A) coated to red blood cells (RBC) we demonstrate that the increase of activation measured at 10xg is due to a simultaneous activation of T- and B-lymphocytes whereas at 1xg only T-cells are stimulated. Conversely, activation of T-cells by chemical modification of the membrane with sodium periodate is depressed at 10xg. Secondly, experiments performed in the centrifuge as well as in the clinostat with Friend, K-562, and hybridoma cells show that each cell line develops its own adaptation reaction to gravitational stress.

B-Lymphocytes↗
PubMed1988

Effect of long-term physical exercise on lymphocyte reactivity: similarity to spaceflight reactions.

The response of critical immunological parameters in seven athletes to the sustained physical stress of marathon running was assessed. Variables analysed were the responsiveness of lymphocytes (measured as mitogenic response to concanavalin A), the numbers of lymphocytes, their subsets, and leukocyte numbers. In addition, blood levels of cortisol, epinephrine, and norepinephrine were determined. After the run, lymphocyte responsiveness was severely depressed to 1-70% of the resting values, even though the lymphocyte counts did not change. Leukocyte counts were elevated 2.8-fold. No dramatic changes were found within the lymphocyte subsets, although an increase in pan T-cells and the helper/inducer subset 2 d after the run was significant. In addition, the numbers of B-cells decreased significantly. No change was observed within the suppressor/cytotoxic subset. Cortisol increased 2.1-fold, epinephrine 3.2-fold and norepinephrine 2.7-fold. All these parameters returned to baseline values within 2 d. These data were compared with data obtained during and after spaceflight. We conclude that prolonged physical stress of marathon running induces changes in immunological responsiveness that are strikingly similar to those arising from the stress of spaceflight.

Epinephrine↗
PubMed1987

Pharmacokinetics of enteric-coated aspirin and inhibition of platelet thromboxane A2 and vascular prostacyclin generation in humans.

We evaluated whether an enteric-coated aspirin formulation showed a "presystemic" component in its antiplatelet effect and if so would spare vascular cyclooxygenase. In six healthy volunteers, 30 to 45 minutes after ingestion of 325 mg enteric-coated aspirin, platelet thromboxane A2 generation was inhibited by about 20% before any drug could be detected in the peripheral venous blood. A further decline in thromboxane A2 generation occurred with appearance of aspirin in blood between 60 and 240 minutes. No presystemic component could be detected after 325 mg aspirin tablets. Ten patients undergoing saphenectomy received 325 mg of either aspirin tablet or enteric-coated aspirin; 12 hours later platelet thromboxane A2 and peripheral vascular prostacyclin generation were significantly reduced by 98% and 58%, respectively. The effects of the two aspirin formulations were not different. Aspirin formulations with "presystemic" component in their antiplatelet effect may not necessarily result in sparing of peripheral vascular cyclooxygenase.

Adult↗
PubMed1986

Surgical treatment for aggressive giant keratoacanthoma of the face.

A case of aggressive giant keratoacanthoma on the right temple region is described. Histopathologic examination was not definitive for keratoacanthoma, so that clinical considerations were helpful for diagnosis. The neoplasm was treated successfully with surgical excision and immediate repair with skin graft, in spite of one narrow peripheral area of residual disease on the wound surface after resection.

Aged↗
PubMed1986

Effects of hypergravity on "whole-blood" cultures of human lymphocytes.

The purpose of this paper is to present a detailed description of the effects of hypergravity on the mitogenic response of human lymphocytes to concanavalin A. The effect on cultures of lymphocytes isolated from peripheral blood are compared with those on whole-blood cultures obtained by diluting fresh blood with culture medium 1:10. Whole-blood cultures of lymphocytes from crew members will be investigated inflight on the Spacelab missions D-1 in 1985 and SLS-1 in 1987. In hypergravity there is an increase in lymphocyte activation of up to 500%. A similar increase can be induced by pre-incubating the cultures in hypergravity prior to exposure to concanavalin A at 1 G. The effect is less evident in cultures of isolated lymphocytes. The influence of autologous plasma and erythrocytes has also been investigated. Plasma and hypergravity have a synergistic and positive effect on lymphocyte activation, i.e. cultures of separated lymphocytes show the highest activation when incubated at 10 G and supplemented with autologous plasma. Conversely, erythrocytes depress lymphocyte activation.

Adaptation, Physiological↗
PubMed1985

Differential salicylate-aspirin interaction on vascular prostacyclin and platelet thromboxane synthesis in patients undergoing saphenectomy.

We studied the ability of salicylate to counteract the effect of aspirin on platelet thromboxane synthesis and prostacyclin formation in venous tissue in patients undergoing saphenectomy. A single intravenous dose of 40 mg aspirin completely blocked thromboxane formation and reduced prostacyclin to about 43% of the control values. When salicylate (1000 mg po) corresponding in anesthetized subjects to blood levels of 25.9 +/- 5 micrograms/ml was administered before aspirin, vascular prostacyclin was no longer inhibited, whereas platelet thromboxane was still significantly blocked. These results suggest that the combination of salicylate with aspirin at an appropriate dose ratio may result in almost complete dissociation of the drug's effect on platelets and vessels in man.

6-Ketoprostaglandin F1 alpha↗
PubMed1981

[New trends in the treatment of trophic sequelae post-phlebitic syndrome].

Authors analyses most recent concepts on pathogenesis of trophic changes in post-phlebitic syndrome: particularly they consider the role of extravascular fibrin deposition, in patients with depressed plasmatic fibrinolytic activity. In this patients, according to recent reports, it seems useful a fibrinolytic therapy to improve trophic conditions of the post-phlebitic limb, particularly in respect to dermatoliposclerosis. Authors refer their experience on a double blind study with stanozolol an anabolizing steroid with fibrinolytic activity: in all treated patients good clinical results were obtained; however no enhancement of plasmatic fibrinolytic activity was demonstrated.

Adult↗