Tissue therapeutic window

Fig. 9.2 a The depth of light penetration into tissue as a funetion of irradiation wavelength, data taken from [10,11]. The range liom 700-950 mn is called tissue therapeutic window due to the minimal abscnbance of biological tissues in this range, b The absorption spectra of the first generation photosensitiser Photo in as compared to the second generation photosensitiser Verteporfin... 

From this we concluded that LMWPs are potentially suitable to serve as renal-specific drug carriers a drug-LMWP conjugate will be rapidly removed from the circulation and the drug can be intra-renally released. Consequently, major distribution to extra-renal tissue and related unwanted effects elsewhere in the body can, in principle, be avoided. It is assumed that secondary redistribution of the generated drug from the kidney is relatively slow so that systemic concentrations remain below the therapeutic window for extra-renal effects. 

Abundant epidemiological data indicate that tumors that overexpress EGFR and/or HER-2 exhibit a worse outcome than tumors that do not overexpress these receptors. In addition, inhibition of these receptors with monoclonal antibodies has been shown to reverse transformation in preclinical models. Moreover, the measurable overexpression of EGFR and HER-2 in tumor diagnostic tissue and the lack of an obvious role for these tyrosine kinases in normal host tissues, all together, support the notion that these tumor cell surface molecules provide a therapeutic window that can be exploited in the treatment of carcinomas that overexpress EGFR and/or HER-2. 

Given the numerous drawbacks associated with the approaches discussed earlier and the obvious advantage offered by the stent as a drug delivery platform, CDD via DES offers the potential to circumvent these problems by providing localized, sustained release of drug within the required therapeutic window. The delivery of drugs directly to the tissues affected by PCI minimizes the impact on nontarget tissues,... 

The specific choice of treatments to be used in combination with hypothermia could be based on a variety of different approaches. First, there could be a direct synergistic effect between hypothermia and the other proposed treatment modality, presumably as a result of a complementary mode of action. For example, combining hypothermia with thrombolytic therapy might be an appropriate pairing in which the hypothermia prolongs the therapeutic window for subsequent definitive reperfusion. Similarly, hypothermia could be used just after thrombolysis, to prevent reperfusion induced injury and prolonging the viability of injured but not irreversibly damaged tissue. 

Currently, the only treatment of patients with acute ischemic stroke is thrombolysis and restoration of blood flow [3,6,7]. Only a fraction of stroke patients benefits from this therapy [3,6,7], Therapeutic recanalization of an occluded cerebral artery is a risky option that can be applied only in the case of selected patients. The main limitation of cerebral thrombolysis is the narrow, 3-hour therapeutic window during which the thrombolytic agent has to be administered to be effective. Beyond this time limit, its effectiveness is neutralized by the high risk of cerebral hemorrhage [7], In acute stroke, only a small fraction of patients benefit from intravenous administration of recombinant tissue plasminogen activator, which is the only drug with proven effectiveness in reducing the size of infarct in humans [6],... 

Sodium fluoride (NaF) promotes the proliferation and activity of osteoblasts and is classified as a nonhormonal bone-forming agent. Because treatment with NaF induces bone formation, it is essential that this therapy be coupled with oral calcium supplementation (1,000 mg/day). Additionally, NaF exhibits moderate antiresorptive activity, because it inhibits osteoclastic activity when it is absorbed into the bone matrix. In the treatment of osteoporosis, the therapeutic window for this agent is fairly narrow Doses less than 45 mg/day are subtherapeutic, and doses in excess of 75 mg/day impair bone mineralization. In addition, the bone that is formed in the presence of NaF is neither as well mineralized nor as strong as normal bone tissue. In fact, some... 

Porphyrin molecules form stable complexes with lanthanide ions, these complexes have intensive absorption in a visible range of spectrum. Erbium, ytterbium and neodymium complexes are characterized by a 4f-luminescence in near IR-range of spectrum [1]. The most studied complexes with porphyrins are ytterbium complexes since Yb has smaller ionic radius in comparison with lanthanum (radius of Yb ion is 1.01 A), which determines higher stability of these metallocomplexes. Distinctive feature of Yb porphyrin complexes is a characteristic narrow and rather intensive luminescence band located in the IR-range at 975-985 nm, in so-called therapeutic window of tissue transparency. ... 

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