Dose-Dependent Prevention of Fibrosis in Aorta of Salt-Loaded Stroke-Prone Spontaneously Hypertensive Rats by Combined Delapril and Indapamide treatment.

Combined treatment with the angiotensin-converting enzyme (ACE) inhibitor delapril and the diuretic indapamide prevented vascular damage in vital organs of salt-loaded stroke-prone spontaneously hypertensive rats (SHRsp). Whether the changes occurring after long-term hypertension could also be modulated in large arteries was investigated. Two-month-old SHRsp were salt loaded and treated with the drug regimen until they reached 50 +/- 10 mortality or around midlife. In a first experiment, delapril (12 mg/kg) and indapamide (1 mg/kg) were administered daily separately or in combination. In the second dose-finding experiment, delapril (6, 3, 1.5 mg/kg) and indapamide (0.5, 0.25, 0.125 mg/kg) in decreasing dose combinations were analyzed. Ultrastructural, histomorphometric, and biochemical studies were performed on the thoracic aorta. When compared with delapril (12 mg/kg) or indapamide (1 mg/kg) administered individually for 5 months, the combination 12 + 1 mg/kg was able to prevent the increase in extracellular matrix deposition observed in other treatment groups, as assessed by histomorphometry or 4-OH-proline biochemical determination. In the second experiment, a half-dose (delapril 6 mg/kg + indapamide 0.5 mg/kg) combination was similarly effective in counteracting fibrosis, but the other doses progressively failed. In the first experiment, the combination had a stabilizing effect on hypertension and stimulated diuresis. In the second experiment, arterial blood pressure values and sodium balance were not consistently affected by the treatments that antagonized fibrosis (i.e., delapril 6 mg/kg + indapamide 0.5 mg/kg and, less efficiently, delapril 3 mg/kg + indapamide 0.25 mg/kg). These results suggest that indapamide interacts with ACE inhibitors to limit aortic fibrosis independent of any well-established mechanism

Cutting edge: extracellular high mobility group box-1 protein is a proangiogenic cytokine.

The chromosomal high mobility group box-1 (HMGB1) protein acts as a proinflammatory cytokine when released in the extracellular environment by necrotic and inflammatory cells. In the present study, we show that HMGB1 exerts proangiogenic effects by inducing MAPK ERK1/2 activation, cell proliferation, and chemotaxis in endothelial cells of different origin. Accordingly, HMGB1 stimulates membrane ruffling and repair of a mechanically wounded endothelial cell monolayer and causes endothelial cell sprouting in a three-dimensional fibrin gel. In keeping with its in vitro properties, HMGB1 stimulates neovascularization when applied in vivo on the top of the chicken embryo chorioallantoic membrane whose blood vessels express the HMGB1 receptor for advanced glycation end products (RAGE). Accordingly, RAGE blockade by neutralizing Abs inhibits HMGB1-induced neovascularization in vivo and endothelial cell proliferation and membrane ruffling in vitro. Taken together, the data identify HMGB1/RAGE interaction as a potent proangiogenic stimulus

Innovation letter - The present and future of space law

Rapid developments taking place in the space sector present both opportunities and risks. The underlying principles of international space law remain valid today. However, there is much need for new regulations and solutions to address the myriad emerging issues resulting from the new realities and prospects of space exploration and utilisation. While soft law is a valuable tool, it cannot be the only answer. The law must uphold the protection of the common interests of humanity, and doing so will not impede but rather promote good industrial and commercial endeavours by private entities

The Treaty on the Prohibition of Nuclear Weapons: A Promise, a Threat or a Flop?

On 7 July 2017 a UN Conference, convened in New York by the General Assembly, adopted a Treaty on the Prohibition of Nuclear Weapons, providing for the first total ban on these weapons intended to be global in scale. The Treaty was opened for signature on 20 September 2017. The process and its outcome, were, however, firmly opposed by nuclear-weapon States and by NATO countries, including Italy: they refused to take part in the effort, fearing that it could definitively undermine the stability of the non-proliferation architecture built upon the 1967 Non-Proliferation Treaty. In reality, the Treaty is consistent with the ultimate purpose of the NPT regime, and the obligations assumed by States under the NPT remain untouched. Its main deficiencies relate to its verification apparatus, and it would be advisable to remedy them through future negotiations. Whether this instrument will enter into force is not clear, although it has the potential to acquire, and surpass, the fifty ratifications necessary. However, the absence of support from nuclear-weapon States risks rendering it irrelevant. Nevertheless, it seems plausible that broad support for this new regime, from non-nuclear-weapons States, as well as from civil society, could contribute to exerting pressure towards the adoption of concrete steps in the nuclear disarmament agenda

Il parere della Corte internazionale di giustizia del 19 luglio 2024 sulle conseguenze giuridiche delle politiche e pratiche di Israele nel Territorio palestinese occupato, inclusa Gerusalemme est

Il parere della Corte internazionale di giustizia del 19 luglio 2024 interviene in una fase drammatica della crisi mediorientale, ma non si occupa dell’assalto del 7 ottobre 2023 e delle conseguenze che la reazione israeliana sta provocando nella Striscia di Gaza, bensì delle politiche e pratiche di Israele nel Territorio palestinese occupato (TPO) dal 1967 ad oggi, con particolare riferimento alla Cisgiordania ed a Gerusalemme est. L’articolo si sofferma in parti- colare su tre conclusioni raggiunte dalla Corte nel quadro del parere: la prima attiene allo status della Striscia di Gaza, ritenuta tutt’ora soggetta al diritto dell’occupazione; la seconda è la valutazione secondo cui l’occupazione prolun- gata del TPO da parte israeliana è illecita, in conseguenza della politica annessionistica posta in essere da Israele a Gerusalemme est e in Cisgiordania, in violazione dello ius ad bellum nonché del diritto all’autodeterminazione del popolo palestinese; la terza attiene alla rilevazione di una politica di segregazione adottata da Israele nel TPO ai danni della popolazione palestinese. Viene sottolineata l’importanza delle valutazioni effettuate dalla Corte e al contempo sono evidenziati taluni limiti e lacune nel ragionamento giuridico seguito dalla stessa

Energy cost and parmesan cheese. An overview in the different energy fluxes needed to produce a parmesan wheel

Agriculture is responsible for up to 30% of the greenhouse gases emission, and cattle breeding is the main contributor making up almost 10% of the total. For this reason, this sector is a key player toward a complete decarbonization. To take the proper action to reduce climate impact of cattle breeding, it is necessary to know the energy requirements of the industry. This work focuses on the energy mapping of a parmesan cheese production, with reference to an agricultural company situated in Modena province with about six hundred animals. Knowing the electrical and thermal energy requirements to produce a wheel of cheese gives the possibility to the farmers to identify and reduce the energy wastage as well as starting the implementation of a strategy for fossil fuel substitution. In this study, a comprehensive monitoring campaign is presented together with the proposal of some possible improvements. The analysis showed that, considering the actual situation, about 64 kWh of electrical energy and 94 kWh of thermal energy are needed to produce a parmesan cheese wheel, while the fuel used to feed the agricultural machinery (e.g., tractors) accounts for around 174 kWh. In this context, the implementation of biogas and solar photovoltaic can greatly contribute to reduce the dependence on fossil fuels

Domestic heating: Can hemp-hurd derived pellet be an alternative?

Among the renewable sources, residual woody biomass from agricultural crops is becoming of great interest due to its lower environmental impact and one of the most growing agricultural sector, of the last decade, is the hemp industry which generates several kind of byproducts. In this paper, a blend of 50% of hemp-hurd and 50% of fir sawdust was pulverized and pelletized. The pellets were burned into a domestic pellet stove (9 kWth maximum nominal thermal power output) at different biomass flowrates. To compare results with a commercial-grade pellet, the tests were repeated by fueling the same stove with A2-grade pellets. Results shown that the pellet mixture 50/50 of fir sawdust and hemp-hurd is suitable for the commercial pellet stove used and that the slightly higher amount of ashes (2.7%), compared to pellet A2 (<1.2%), can be handled by the self-cleaning fire chamber. Comparable results were also obtained in regards with the stove global efficiency which ranged from 90.8-92.3% for the hemp pellets and 91-94% for the A2. A significant difference was noted in the biomass flowrate where, during the tests with hemp-hurd pellets a lower value was obtained (-20%) compared to A2. This resulted into lower power input in the stove and lower performances at the same nominal power output